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Genes
Hox
Control of morphogenesis
and differentiation by HOM/Hox genes. Botas, J.
Curr. Opin. Cell Biol. 5 1015-1022
(1993).
- These ancient genes
have conserved their function throughout
evolution in diverse species. Homeotic selector
genes (HOM) in drosophila and nematodes and Hox
genes in vertebrates.
- This family of genes
appear to regulate axial cell fate in the
embryo.
- The genes share
structure organization and
expression.
- The homeobox sequence
is 180 bp with a helix-turn-helix
motif.
- These proteins are
transcription factors which bind to specific DNA
sequences and activate genes.
Murine Development Control Genes, Kessel, M. and
Gruss, P. Science 249 374-379 (1990).
- An early review of the genes, and method of
identifying them, involved in early mouse
development. In particular discusses Homeobox
genes. (homeobox is 183bp encoding a 61 amino
acid DNA-binding domain)
- Gene families
Early
Development
Establishment of the axis in chordates: facts
and speculations, H. Eyal-Giladl, Development
124:2285-2296 (1997)
Somites
Early stages of chick somite development.
Christ, B. and Ordahl, C.P. Anat. Embryol.
191 381-396 (1995).
Heart
(review)
Fashioning the vertebrate heart: earliest
embryonic decisions. M.C. Fishman and M.C. Chien,
Development 124:2099-2117 (1997)
(Mouse)
The allocation of epiblast cells to the
embryonic heart and other mesodermal lineages: the
role of ingression and tissue movement during
gastrulation. Tam, P.P.L. et al., Development
124 1631-1642 (1997).
- Epiblast cells aquire a cardiogenic fate
without ingression through the primitive streak
or movement within the mesoderm. Allocation of
epiblast cells to a mesodermal lineage appears
dependent upon the timing of recruitment to the
primitive streak.
Limbs
Why thumbs are up. Martin,
G.R. Nature 374 410-411 (1995).
- Reviews a paper in
this issue of Nature concerning Wnt-7a
expression in the limb, but also summarizes the
other polarizing signals in the
limb.
Nervous
System
CNS
Determination events in the nervous system of
the vertebrate embryo. Superieure, L.B. and Wassef,
M. Curr Opin in Genetics and Development 5
450-458 (1995).
Evidence for multi-site closure of the neural
tube in humans. Van Allen, M. I. et al., American J
of Medical Genetics 47 723-43 (1993).
- Multisite neural tube (NT) closure has been
demonstrated in chicken and mouse embryos.
- This study looks at neural tube defects
(NTDs) in humans and the role of multisite
closure.
- Genetic variations of NT closures sites
occur in mice and are evident in humans, e.g.,
familial NTDs with Sikh heritage (closure 4 and
rostral 1), Meckel-Gruber syndrome (closure 4),
and Walker-Warburg syndrome (2-4 neuropore,
closure 4).
- Environmental and teratogenic exposures
frequently affect specific closure sites, e.g.,
folate deficiency (closures 2, 4, and caudal 1)
and valproic acid (closure 5 and
canalization).
ABNORMALITIES
Disorders of the central nervous system. Paidas,
M. J. and Cohen, A. Seminars in Perinatology
18 266-282 (1994).
- Review article of most commonly seen CNS
abnormalities.
- Dandy-Walker Syndrome, Fetal Diseases,
Holoprosencephaly, Hydrocephalus, Neural Tube
Defects, Spina bifida.
Vulnerable periods and processes during central
nervous system development. Rodier, P. M.
Environmental Health Perspectives 102 Suppl
2 121-4 (1994).
- The developing CNS lacks a blood brain
barrier.
- Known teratogens indicate that differential
doses to the developing vs mature brain are not
the major factor in differential
sensitivity.
- Most agents seem to act on processes that
occur only during development: cell
proliferation, migration, and
differentiation.
- The most important of these is probably the
fact that nervous system development takes much
longer than development of other organs, making
it subject to injury over a longer period.
Linkage of a human brain malformation, familial
holoprosencephaly, to chromosome 7 and evidence for
genetic heterogeneity. Muenke, M. et al., PNAS
91 8102-6 (1994).
- Holoprosencephaly (HPE) is a common
malformation of the developing forebrain and
midface characterized by incomplete penetrance
and variable expressivity.
- These results show that a gene for autosomal
dominant HPE is located in a chromosomal region
(7q36) known to be involved in sporadic HPE with
visible cytogenetic deletions.
Mutations in the human Sonic Hedgehog gene cause
holoprosencephaly. Roessler, E. et al., Nature
Genetics 14 357-60 (1996).
- Holoprosencephaly (HPE) is a common
developmental defect of the forebrain and
frequently the midface in humans, with both
genetic and environmental causes.
- HPE has a prevalence of 1:250 during
embryogenesis and 1:16,000 newborn infants.
- Involves incomplete development and
septation of midline structures in the central
nervous system (CNS) with a broad spectrum of
clinical severity.
- Alobar HPE, the most severe form which is
usually incompatible with postnatal life,
involves complete failure of division of the
forebrain into right and left hemispheres and is
characteristically associated with facial
anomalies including cyclopia, a primitive nasal
structure (proboscis) and/or midfacial
clefting.
- The molecular basis underlying HPE is not
known, although teratogens, non-random
chromosomal anomalies and familial forms with
autosomal dominant and recessive inheritance
have been described.
- HPE3 on chromosome 7q36 is one of at least
four different loci implicated in HPE.
- Identification of human Sonic Hedgehog (SHH)
as HPE3-the first known gene to cause HPE.
-
Neural
Crest
Contribution of
early-emigrating midbrain crest cells to the dental
mesenchyme of mandibular molar teeth in rat
embryos.
Imai, H. et al.,
Developmental Biology 176 151-65
(1996).
- rat
- Reciprocal
interactions between the epithelium and
mesenchyme in the first pharyngeal arch form
teeth.
- This paper does
labelling studies in the rat to observe that
early-emigrating posterior midbrain crest cells
(at the end of the 4-somite stage) predominantly
migrated to the region where tooth buds
(mandibular molar) normally develop.
Spatial distribution of
postotic crest cells defines the head/trunk
interface of the vertebrate body: embryological
interpretation of peripheral nerve morphology and
evolution of the vertebrate head. Kuratani, S.
Anatomy & Embryology 195 1-13
(1997).
- chicken
- The migration pathways
and spatial distribution of neural crest cells
largely depend on the embryonic
architecture.
- Postotic crest is
located at the intermediate level between the
trunk and the head, giving rise to both the
cephalic and trunk crest cells. Its cephalic
components circumpharyngeal crest cells, are
distributed only rostral to the S-shaped
interface.
Teratogens
Vulnerable periods and processes during central
nervous system development. Rodier, P. M.
Environmental Health Perspectives 102 Suppl
2 121-4 (1994).
- The developing CNS lacks a blood brain
barrier.
- Known teratogens indicate that differential
doses to the developing vs mature brain are not
the major factor in differential
sensitivity.
- Most agents seem to act on processes that
occur only during development: cell
proliferation, migration, and
differentiation.
- The most important of these is probably the
fact that nervous system development takes much
longer than development of other organs, making
it subject to injury over a longer period.
Retinoids as teratogens. Soprano, D. R. and
Soprano, K. J. Annual Review of Nutrition 15
111-32 (1995).
- Review of Vitamin A as a necessary nutrient
in the diet.
- Reviews fetal malformations associated with
maternal ingestion of natural and synthetic
retinoids in both experimental animals and
humans.
Review of the role of potential teratogens in
the origin of human nonsyndromic oral clefts.
Wyszynski, D. F. and Beaty, T. H. Teratology
53 309-17 (1996).
- Oral clefts occur approx 1 every 1,000
caucasian newborns.
- This is a review of literature on
environmental exposures potentially associated
with non-syndromic oral clefts.
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Introduction