Difference between revisions of "Developmental Signals - Homeobox"

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Vertebral element ossification between species.<ref name="PMID20956304"><pubmed>20956304</pubmed>| [http://www.pnas.org/content/107/44/18903.full Proc Natl Acad Sci U S A.]</ref>
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Vertebral element ossification between species.<ref name="PMID20956304"><pubmed>20956304</pubmed>| [http://www.pnas.org/content/107/44/18903.full Proc Natl Acad Sci U S A.]</ref>
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Chicken model of Hox in paraxial mesoderm precursors in the epiblast/tail-bud during axis elongation<ref><pubmed>25719209</pubmed>| [http://elifesciences.org/content/4/e04379 Elife.]</ref>
  
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Revision as of 16:09, 6 September 2015

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Introduction

Proposed Hox protein classification
Proposed Hox protein classification[1]

The family of homeobox (Hox) proteins has been a focus of research for over 30 years. This family of genes were also the basis of the embryo patterning studies that led to the Nobel Prize in Medicine 1995. We now know that in addition to whole embryo axes patterning, this family of genes has many roles in establishing pattern throughout the embryo in different tissues and organs.

There has recently been a revival of an earlier theory[2] that Hox expression during vertebrate pattern formation is linked to the process of segmentation of paraxial mesoderm during somitogenesis.[3]


This signalling pathway has also been implicated in many developmental abnormalities and diseases.

Fly wild-type head.jpg Fly antennapedia head.jpg
Fly wild-type head Fly antennapedia head


Factor Links: AMH | hCG | BMP | sonic hedgehog | bHLH | HOX | FGF | FOX | Hippo | LIM | Nanog | NGF | Nodal | Notch | PAX | retinoic acid | SIX | Slit2/Robo1 | SOX | TBX | TGF-beta | VEGF | WNT | Category:Molecular

| Category:Hox

Some Recent Findings

Model Hox10 kidney development
Mouse Hoxa5 expression
Mouse Hoxa5 expression (E12.5)[4]
  • Homeobox Genes of Caenorhabditis elegans and Spatio-Temporal Expression[5] "We show that, out of 103 homeobox genes, 70 are co-orthologous to human homeobox genes. 14 are highly divergent, lacking an obvious ortholog even in other Caenorhabditis species. One of these homeobox genes encodes 12 homeodomains, while three other highly divergent homeobox genes encode a novel type of double homeodomain, termed HOCHOB. To understand how transcription factors regulate cell fate during development, precise spatio-temporal expression data need to be obtained. Using a new imaging framework that we developed, Endrov, we have generated spatio-temporal expression profiles during embryogenesis of over 60 homeobox genes, as well as a number of other developmental control genes using GFP reporters." Worm Development
  • A Hox regulatory network of hindbrain segmentation is conserved to the base of vertebrates[6] "Here, using a novel tool that allows cross-species comparisons of regulatory elements between jawed and jawless vertebrates, we report deep conservation of both upstream regulators and segmental activity of enhancer elements across these distant species. Regulatory regions from diverse gnathostomes drive segmental reporter expression in the lamprey hindbrain and require the same transcriptional inputs (for example, Kreisler (also known as Mafba), Krox20 (also known as Egr2a)) in both lamprey and zebrafish. We find that lamprey hox genes display dynamic segmentally restricted domains of expression; we also isolated a conserved exonic hox2 enhancer from lamprey that drives segmental expression in rhombomeres 2 and 4. Our results show that coupling of Hox gene expression to segmentation of the hindbrain is an ancient trait with origin at the base of vertebrates that probably led to the formation of rhombomeric compartments with an underlying Hox code."
  • Hoxb1b controls oriented cell division, cell shape and microtubule dynamics in neural tube morphogenesis[7] "Hox genes are classically ascribed to function in patterning the anterior-posterior axis of bilaterian animals; however, their role in directing molecular mechanisms underlying morphogenesis at the cellular level remains largely unstudied. ...Hoxb1b regulates mitotic spindle rotation during the oriented neural keel symmetric mitoses that are required for normal neural tube lumen formation in the zebrafish."
  • Developmental Dynamics special issue January 2014 Hox/Tale transcription factors in development and disease
  • Evolution of anterior Hox regulatory elements among chordates[8] "The Hox family of transcription factors has a fundamental role in segmentation pathways and axial patterning of embryonic development and their clustered organization is linked with the regulatory mechanisms governing their coordinated expression along embryonic axes. Among chordates, of particular interest are the Hox paralogous genes in groups 1-4 since their expression is coupled to the control of regional identity in the anterior nervous system, where the highest structural diversity is observed. ...Together, our results indicate that during chordate evolution, cis-elements dependent upon Hox/Pbx regulatory complexes, are responsible for key aspects of segmental Hox expression in neural tissue and appeared with urochordates after cephalochordate divergence."
  • Hox10 Genes Function in Kidney Development in the Differentiation and Integration of the Cortical Stroma [9] "Consistent with loss of cortical stromal cell function, Hox10 mutant kidneys display reduced and aberrant ureter branching, decreased nephrogenesis. These data therefore provide critical novel insights into the cellular and genetic mechanisms governing cortical cell development during kidney organogenesis. These results, combined with previous evidence demonstrating that Hox11 genes are necessary for patterning the metanephric mesenchyme, support a model whereby distinct populations in the nephrogenic cord are regulated by unique Hox codes, and that differential Hox function along the AP axis of the nephrogenic cord is critical for the differentiation and integration of these cell types during kidney organogenesis."
  • Proposed Hox protein classification[1]"Our classification scheme offers a higher-resolution classification that is in accordance with phylogenetic as well as experimental data and, thereby, provides a novel basis for experiments, such as comparative and functional analyses of Hox-proteins."
  • Homeobox A7 up-regulation of epidermal growth factor receptor expression in human granulosa cells[10]"Our present study reveals a novel mechanistic role for HOXA7 in modulating granulosa cell proliferation via the regulation of EGFR. This finding contributes to the knowledge of the pro-proliferation effect of HOXA7 in granulosa cell growth and differentiation."
  • Hoxa5 transcriptional complexity in the mouse embryo[4]Our observation that the Hoxa5 larger transcripts possess a developmentally-regulated expression combined to the increasing sum of data on the role of long noncoding RNAs in transcriptional regulation suggest that the Hoxa5 larger transcripts may participate in the control of Hox gene expression.
More recent papers
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Search term: Hox

<pubmed limit=5>Hox</pubmed>

Classification

Proposed Hox protein classification.jpg
Proposed Hox protein classification[1]

Human Hox

Ideograms Human homeobox genes

Chromosomal Distribution of Human Homeobox Genes[11]


Functions

Developmental patterning signal.

Neural

Hindbrain neural crest migration.jpg

Hindbrain neural crest migration and Hox expression pattern[12]


A schematic diagram of a chick head at embryonic day two (Hamburger Hamilton Stages), showing pathways of neural crest migration in the chick and mouse embryo and patterns of Hox gene expression in the pharyngeal arches. Hox genes are expressed in neural crest cells, which emigrate predominantly from even-numbered rhombomeres into the pharyngeal (branchial) arches generating skeletal tissues and cranial ganglia.


Note that the first pharyngeal arch is free of Hox expression.

Legend

  • PA - pharyngeal arch
  • Md - mandibular part of pharyngeal arch 1
  • Mx - maxillary part of pharyngeal arch 1
  • OV - otic vesicle
  • r - rhombomere

Adapted by permission from Macmillan Publishers Ltd: Nature Reviews Neuroscience (<pubmed>17948031</pubmed>), copyright (2007)

Links: Neural System Development | Neural Crest Development

Axial Skeleton

Vertebra ossification sequence.jpg

Vertebral element ossification between species.[13]

Hox 3 phase model.jpg

Chicken model of Hox in paraxial mesoderm precursors in the epiblast/tail-bud during axis elongation[14]


Links: Somitogenesis | Axial Skeleton Development

Limb

Limb patterning factors 08.jpg

Mouse Limb Patterning Fgf and Hox Expression[15]

Fgf and Hox expression in E10.5 to 10.75 wild-type embryonic forelimb autopod, compared to future E14.5 digit arrangement.

Hoxa gene expression in limb bud 01.jpg

Expression of Hoxa4, Hoxa9, Hoxa10, Hoxa11, Hoxa11 antisense (Hoxa11as), and Hoxa13 in E12.5 limb buds.[16]


Links: Limb Development

Other

Signaling Pathway

Additional Images

References

  1. 1.0 1.1 1.2 <pubmed>20520839</pubmed>| PLoS One
  2. Meinhardt H. Models For Biological Pattern Formation. Academic Press; 1982.
  3. <pubmed>25785959</pubmed>
  4. 4.0 4.1 <pubmed>20485555</pubmed>| PLoS One
  5. <pubmed>26024448</pubmed>| PLoS One.
  6. <pubmed>25219855</pubmed>
  7. <pubmed>24449840</pubmed>
  8. <pubmed>22085760</pubmed>
  9. Yallowitz AR, Hrycaj SM, Short KM, Smyth IM, Wellik DM (2011) Hox10 Genes Function in Kidney Development in the Differentiation and Integration of the Cortical Stroma. PLoS ONE 6(8): e23410. PMID 21858105 PloS One
  10. <pubmed>20540809</pubmed>| Reprod Biol Endocrinol.
  11. <pubmed>17963489</pubmed>| BMC Biol.
  12. <pubmed>17948031</pubmed>
  13. <pubmed>20956304</pubmed>| Proc Natl Acad Sci U S A.
  14. <pubmed>25719209</pubmed>| Elife.
  15. <pubmed>20386744</pubmed>| PMC2851570 | PLoS Genet.
  16. <pubmed>24465181</pubmed>| PLoS Biol.


Reviews

<pubmed>20435029</pubmed> <pubmed>19651304</pubmed> <pubmed>15944185</pubmed> <pubmed>11604126</pubmed>

Articles

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July 2010 "hox" All (3509) Review (545) Free Full Text (1453)

Search Pubmed Now: Hox Homeobox

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Cite this page: Hill, M.A. (2020, April 6) Embryology Developmental Signals - Homeobox. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Developmental_Signals_-_Homeobox

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© Dr Mark Hill 2020, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G