Sex determination (male/female) at the biological level is determined by the presence or absence of the Y chromosome.
Initially, we did not know what this factor was and it was designated the "testis determining factor" (TDF). We now know (since 1990) that TDF is the protein product encoded by the SRY gene on the Y chromosome. Without this gene/protein the potential sex is female (see Male below).
For some time, female was considered the "default" sex in the absence of SRY, we now know this is not the case, with several genes specifically required for ovary formation. In females, sex determination involves at least one X chromosome gene, DAX1 encoding a nuclear hormone receptor.
Another critical genetic issue is related to the presence of two X chromosomes, "gene dosage", and in the case of mammals this is regulated by inactivating one of those X chromosomes in each and every cell (see Female below).
UNSW Embryology: Week 1 Development
Sry was discovered (1990) by studying a human XY female, resulting from a deletion in the Y chromosome that did not allow testis development. Subsequent mapping of this deletion allowed isolation and characterization of the SRY gene.
There is a suggestion that SRY may allow testes development by acting to inhibit DAX1, which is expressed in the indifferent gonad at the same time. The mechanism of an inhibitor inhibiting and inhibitor is seen in some other developing systems.
SRY encodes: encodes a 204 amino acid protein (Mr 23884 Da) that is a zinc-finger transcription factor. Transcription factors bind to specific sites of DNA and regulates the transcription (expression) of other genes, we still do not know all the genes SRY regulates.
SRY is expressed: when testes begin to form, in gonadal tissue and does not require the presence of germ cells.
Notes: The Y chromosome is much smaller than the X chromosome and by definition, cannot contain important genes for other cellular functions. Nomenclature, capital letters are used for human genes (SRY) and lower case letters are used for the equivalent genes in other species (sry).
Historic drawing of Adult Testis
In contrast to the Y chromosome, the X chromosome contains about 5% of the haploid genome and encodes house-keeping and specialized functions. The genetic content of the X chromosome has been strongly conserved between species.
An early discovery (1961) was that in order to have correct levels of X chromosome gene/protein expression (gene dosage), females must "inactivate" a single copy of the X chromosome in each and every cell. The initiator of the X inactivation process was discovered (1991) to be regulated by a region on the inactivating X chromosome encoding an X inactive specific transcript (XIST), that acts as RNA and does not encode a protein. Furthermore X inactivation occurs randomly throughout the embryo, generating a mosaic of maternal and paternally derived X chromosome activity in all tissues and organs.
Notes: A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Brown CJ, Ballabio A, Rupert JL, Lafreniere RG, Grompe M, Tonlorenzi R, Willard HF Nature 1991 Jan 3;349(6304):38-44 Current thinking is that it binds to the X Chromosome and is involved in it's translocation to the nuclear periphery. It now appears that XIST appears to initiate X inactivation and it is the methylation of the inactive X genes that maintains inactivity.
Historic drawing of Adult Ovary
Primordial Germ Cells (PGCs) are thought to be the first population of cells to migrate through the primitive streak in early gastrulation. This population of cells then lie at thehindgut yolk sac junctional region and later migrate into the germinal ridge in early embryonic development.
It is not the primordial germ cells which respond to SRY presence or absence, but the supporting cells within the developing gonad.
Link to next page in this Practical - Early Embryo (Week 5 stage 13/14)
The process of gonad formation.
Use the alphabetical list below to find definitions of terms that are new to you or use the Google search window to search UNSW Embryology site.
amnion - An extraembryonic membrane ectoderm and extraembryonic mesoderm in origin and forms the innermost fetal membrane, produces amniotic fluid. This fluid-filled sac initially lies above the trilaminar embryonic disc and with embryoic disc folding this sac is drawn ventrally to enclose (cover) the entire embryo, then fetus. The presence of this membane led to the description of reptiles, bird, and mammals as amniotes. (More? Placenta Notes | Week 2 Notes)
amniotic fluid - The fluid that fills amniotic cavity totally encloses and cushions the embryo. Amniotic fluid enters both the gastrointestinal and respiratory tract following rupture of the buccopharyngeal membrane. The late fetus swallows amniotic fluid.
Anti-Mullerian Hormone - (AMH, Mullerian Inhibiting Substance, MIS) A secreted factor (transforming growth factor-beta, TGF-beta superfamily) that regulates gonadal and genital tract development. Inhibits paramesonephric (Mullerian) duct development in males. (More? Male | OMIM - AMH)
autosomal - The term decribing all the chromosomes that contribute to a cell's genetic material, except for the sex chromosomes X, Y. (More? DNA Notes)
autosomal inheritance - Some hereditary diseases are described as autosomal which means that the disease is due to a DNA error in one of the 22 pairs that are not sex chromosomes. Both boys and girls can then inherit this error. If the error is in a sex chromosome, the inheritance is said to be sex-linked. (More? DNA Notes)
axial process - The precursor to the notochord. In the early embryo (week 3) epiblast structure extending from the primitive node (Hensens node) crainally, which will eventuall differentiate to for the notochord, the mesoderm structure that later replaces the axial process. (More? notochord | Neural Notes | Week 3 Notes)
buccal - (Latin, bucca = cheek) A term used to relate to the mouth (oral cavity). (More? GIT Notes)
buccopharyngeal membrane - (oral membrane) (Latin, bucca = cheek) A membrane which forms the external upper membrane limit (cranial end) of the early gastrointestinal tract (GIT). This membrane develops during gastrulation by ectoderm and endoderm without a middle (intervening) layer of mesoderm. The membrane lies at the floor of the ventral depression (stomadeum) where the oral cavity will open and will breakdown to form the initial "oral opening" of the gastrointestinal tract. The equivilent membrane at the lower end of the gastrointestinal tract is the cloacal membrane. (More? GIT Notes | Face Notes | Head Notes)
coelom - Term used to describe a space. There are extraembryonic and intraembryonic coeloms that form during vertebrate development. The single intraembryonic coelom will form the 3 major body cavities: pleural, pericardial and peritoneal. (More? Coelom Notes)
DAX1 - Acronym for Dosage sensitive sex reversal (DSS), Adrenal hypoplasia congenita (AHC) critical region on the X chromosome, gene 1 , (gene NR0B1) is a nuclear hormone receptor involved in female ovary development. (More? Urogenital Notes | OMIM Entry DAX1)
DAZL - Acronym for DAZ-like due to homology to DAZ (Deleted in AZoospermia), a gene on the long arm of the Y chromosome that is frequently deleted in infertile men with nonobstructive azoospermia. (More? Spermatogenesis | OMIM Entry DAZL)
endoderm - (Greek, endo = inside + derma = skin) One of the initial 3 germ cell layers, formed by the process of gastrulation. The endoderm forms as a cuboidal epithelium and contributes not only to the trilaminar embryo, but also lines the yolk sac. It will form the entire epithelial lining of the gastrointestinal tract (GIT), contribute to the accessory organs of GIT and also forms the epithelial lining of the respiratory tract. Note that in the GIT it contributes both epithelium and the associated epithelial glands. In humans, endoderm forms during week 3 of development. (More? Week 3 - Gastrulation | Week 3 Notes)
estrogens - Sex hormone found in both male and female. In the female, this hormone is produced by the ovaries and is responsible for development of secondary feminine sex characteristics. Together with progesterone these hormones also regulate changes that occur each menstral cycle. In the male, Leydig cells produce estrogen into the rete testis fluid at variable levels in different species. During male embryonic development exposure to high levels of estrogen can lead to genital abnormalities. (More? Human Menstrual Cycle)
first trimester - Clinical term used to describe and divide human pregnancy period (9 months) into three equal parts of approximately three calendar months. The first trimester corresponds approximately to embryonic development (week 1 to 8) of organogenesis and early fetal. The second and third trimester correspond to the fetal period of growth in size (second trimester) and weight (third trimester), as well as continued differentiation of existing organs and tissues. (More? Embryo Stages | Human Fetal Period | Development Week by Week)
gametes - (Greek, gamos = marriage) A specialized reproductive cell through which sexually reproducing parents pass chromosomes to their offspring; a sperm or an egg. (More? Week 1 Notes)
gameteogenesis - The production of either the haploid germ cells of spermatazoa (male) or eggs (female) (More? Week 1 Notes)
gastrula - (Greek, gastrula = little stomach) A stage of an animal embryo in which the three germ layers have just formed. (More? Gastrulation)
gastrulation - The process of differentiation forming a gastrula. Term means literally means "to form a gut" but is more in development, as this process converts the bilaminar embryo (epiblast/hypoblast) into the trilaminar embryo (endoderm/mesoderm/ectoderm) establishing the 3 germ layers that will form all the future tissues of the entire embryo. This process also establishes the the initial body axes. (More? Gastrulation)
gene - A DNA sequence that is transcribed as a single unit and encodes a single polypeptide (protein) or a set of closely related polypeptides. There are approximately 20,000-25,000 protein encoding genes in the human genome. In each cell, DNA is found within the nucleus and also within mitochondria. (More? DNA Notes)
genome - The collection of all the DNA in an organism. (More? DNA Notes)
germ layers - The first three cellular layers (ectoderm, mesoderm, and endoderm) that will form all tissues of the embryo. In humans, these layers begin to form during week 3 of development. Term should not be confused with germ cells, which are the oocyte and spermatazoa forming cells. Named originally by Robert Remak (1815 - 1865) a German scientist and embryologist. (More? Week 2 Notes Week 3 Notes | Robert Remak)
gonad - (Greek, gonos = seed) A gamete-producing (germ cell) organ. A non-sexual term which is used to describe both the female ovary and male testis. (More? Week 1 Notes)
intraembryonic coelom - The "horseshoe-shaped" space (cavity) that forms initially in the third week of development in the lateral plate mesoderm that will eventually form the 3 main body cavities: pericardial, pleural, peritoneal. The intraembryonic coelom communicates transiently with the extraembryonic coelom. (More? Coelom Notes | Week 3 Notes)
mesenchyme - Term used to describe the cellular organisation of undifferentiated embryonic connective tissue . Mesenchymal tissue is mainly derived from mesoderm and neural crest, which will form most of the adult connective tissues. This connective tissue organization contrasts with the other main form of cellular organization, epithelial tissue. (More? Musculoskeletal Notes)
mesoderm - The middle layer of the 3 germ cell layers of the embryo. Mesoderm outside the embryo and covering the amnion, yolk and chorion sacs is extraembryonic mesoderm. (More? Musculoskeletal Notes | Week 3 Notes)
neuralation - The general term used to describe the formation of the nervous system. It is often used to describe the early events of differentiation of the central ectoderm region to form the neural plate and all the processes that occur therafter. The nervous system includes the central nervous system (brain and spinal cord) from the neural tube and the peripheral nervous system (peripheral sensory and sympathetic ganglia) from neural crest. (More? Neural Notes | Neural Crest Notes)
neural folds - The central region of the trilaminar embryo ectoderm called the neural plate region folds dorsally, generating two neural folds, which later fuse to form the neural tube. The mid-line depression between the two folds is described as the neural groove. In humans at approximately day 18-19 post-fertilization to form the neural groove, which then fuses to form an initially open at either end hollow neural tube. The neural tube forms the central nervous system (brain and spinal cord). Developmental sequence: neural plate ->(day 18-19) neural groove -> neural tube -> Central Nervous System -> brain and spinal cord. (More? Neural Notes)
neural groove - The second stage in early development of the central nervous system. In the trilaminar embryo (ectoderm, mesoderm, endoderm) the central region of the ectoderm (in the midline above the mesodermal notochord) initially forms a columnar epithelium described as the neural plate. This epithelium will fold dorsally, beginning in humans at approximately day 18-19 post-fertilization to form the neural groove, which then fuses to form an initially open at either end hollow neural tube. The neural tube forms the central nervous system (brain and spinal cord). Developmental sequence: neural plate ->(day 18-19) neural groove -> neural tube -> Central Nervous System -> brain and spinal cord. (More? Neural Notes)
neural plate - The first stage in early development of the central nervous system. In the trilaminar embryo (ectoderm, mesoderm, endoderm) the central region of the ectoderm (in the midline above the mesodermal notochord) initially forms a columnar epithelium described as the neural plate. This epithelium will fold dorsally to form the neural groove, which then fuses to form an initially open at either end hollow neural tube. The neural tube forms the central nervous system (brain and spinal cord). Developmental sequence: neural plate -> neural groove -> neural tube -> Central Nervous System -> brain and spinal cord. (More? Neural Notes)
neural tube - The third stage in early development of the central nervous system. In the trilaminar embryo (ectoderm, mesoderm, endoderm) the central region of the ectoderm (in the midline above the mesodermal notochord) initially forms a columnar epithelium described as the neural plate. This epithelium will fold dorsally to form the neural groove, which then fuses to form an initially open at either end hollow neural tube. The neural tube forms the central nervous system (brain and spinal cord). Developmental sequence: neural plate -> neural groove -> neural tube -> Central Nervous System -> brain and spinal cord. (More? Neural Notes)
neurogenesis - The process of formation of the neural system. This begins with segregation of the neural plate from the ectoderm of the trilaminar embryo by folding to form initially the neural groove, which then fuses to form the neural tube (the central nervous system progenitor, brain and spinal cord) and associated neural crest. (More? Neural Note)
notochord - (axial mesoderm) The rod of cells lying in the midline of the trilaminar embryo mesoderm layer ventral to the neural tube. Thought to have at least 2 early roles in development and later roles in patterning surrounding tissues. 1. Mechanical, influencing the folding of the early embryo; 2. Morphogenic, secreting sonic hedgehog a protein which regulates the development of surrounding tissues (neural plate, somites, endoderm and other organs). In humans, the notochord forms in week 3 and is eventually lost during the formation of the vertebral column. (More? Mesoderm Notes | Neural Notes | Molecular Development- Sonic Hedgehog)
paraxial mesoderm - The two lateral strips of mesoderm lying beside the axial mesoderm (notochord). This mesoderm at the body level will segment into somites, at the head level it remains unsegmented. (More? Musculoskeletal Notes | Week 3 Notes)
somitogenesis The process of segmentation of the paraxial mesoderm within the trilaminar embryo body to form pairs of somites, or balls of mesoderm. A somite is added either side of the notochord (axial mesoderm) to form a somite pair. The segmentation does not occur in the head region, and begins cranially (head end) and extends caudally (tailward) adding a somite pair at regular time intervals. The process is sequential and therefore used to stage the age of many different species embryos based upon the number visible somite pairs. In humans, the first somite pair appears at day 20 and adds caudally at 1 somite pair/90 minutes until on average 44 pairs eventually form. (More? Week 3 - Somitogenesis | Musculoskeletal Notes)
spermatazoa - The male haploid reproductive cell, produced by meiosis in the testis (male gonad). (More? Week 1 - Spermatogenesis)
spermatogenesis - (Greek, genesis = origin, creation, generation) The term used to describe the process of diploid spermatagonia division and differentiation to form haploid spermatazoa within the testis (male gonad). The process includes the following cellular changes: meiosis, reoorganization of DNA, reduction in DNA content, reorganization of cellular organelles, morphological changes (cell shape). The final process of change in cell shape is also called spermiogenesis. (More? Week 1 - Spermatogenesis)
splanchnic mesoderm - Gastrointestinal tract (endoderm) associated mesoderm formed by the separation of the lateral plate mesoderm into two separate components by a cavity, the intraembryonic coelom. Splanchnic mesoderm is the embryonic origin of the gastrointestinal tract connective tissue, smooth muscle, blood vessels and contribute to organ development (pancreas, spleen, liver). The intraembryonic coelom will form the three major body cavities including the space surrounding the gut, the peritoneal cavity. The other half of the lateral plate mesoderm (somatic mesoderm) is associated with the ectoderm of the body wall. (More? Week 3 | Gastrointestinal Tract Notes | Heart Notes )
sry - (Sry, human; Testis-Determining Factor, TDF; Testis-Determining Factor on Y, TDY ) Gene name sex-determining region of Y, the gene locus on the Y chromosome encoding the male "testis determining factor", a protein transcription factor and a member of the high mobility group (HMG)-box family of DNA binding proteins. See also the transcription factor SRY-related protein, SOX9 (SRY-related high-mobility group (HMG) box 9) (More? Molecular Notes | Week 1 Notes | OMIM)
testes - (Latin testis = "witness") The two male gonads (singular testis) where male germ cells (spermatozoa) are generated and also the source of testosterone (male hormone). Embryonically formed from primordial germ cells entering region of the paired mesonephric ducts (Wolffian ducts) which are preserved in male gonad development and lost in females. (More? Genital System - Male)
testis - (Latin testis = "witness", plural testes) The male gonad where male germ cells (spermatozoa) are generated and also the source of testosterone (male hormone). Embryonically formed from primordial germ cells entering region of the paired mesonephric ducts (Wolffian ducts) which are preserved in male gonad development and lost in females. (More? Genital System - Male)
testis-determining factor - (TDF, Sry, Testis-Determining Factor on Y, TDY ) Protein name for the protein transcription factor product of the Sry gene on the Y chromosome responsible for maleness. This protein is a member of the high mobility group (HMG)-box family of DNA binding proteins. See also the transcription factor SRY-related protein, SOX9 (SRY-related high-mobility group (HMG) box 9) (More? Molecular Notes | Week 1 Notes | OMIM)
X chromosome - The female sex chromosome, which following sexual reproduction is inherited from each parent in females, and inherited from the mother in males. This inheritence pattern impacts upon the pattern of genetic disease. (More? X Chromosome)
Xist - The name for a non-translated RNA (18 Kb) that is associated with the inactivated X chromosome in female cells to correct for the double gene dosage, 2 copies of the X chromosome. (More? Molecular Development - X Inactivation | X Chromosome | Week 1 Notes)
X inactivation - Process that occurs in all cells within females, each cell has 2 copies of the X chromosome (one from father and one from mother) one of copy of which is randomly inactivated throughout the entire body in order to maintain gene dosage. (More? Molecular Development - X Inactivation | X Chromosome | Week 1 Notes)
X linked - Term used to refer to genes, and genetic diseases, located on the X chromosome. Therefore more likely to be expressed in males, where there is only a single maternal X chromosome. (More? X Chromosome)
Y chromosome - The male sex chromosome which contains the sry gene producing Testis-Determining Factor required for male phenotype and can only be inherited from father. In humans the chromosome contains 200+ genes and consists of 50 million base pairs. Testis-Determining Factor (TDF; Testis-Determining Factor on Y, TDY ) is a protein transcription factor and a member of the high mobility group (HMG)-box family of DNA binding proteins. See also the transcription factor SRY-related protein, SOX9 (SRY-related high-mobility group (HMG) box 9). (More? Y Chromosome | Molecular Notes | Week 1 Notes | OMIM)