Developmental Signals - Homeobox

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Mouse HOXA5 expression (E12.5)[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.

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

Some Recent Findings

Model Hox10 kidney development
  • Evolution of anterior Hox regulatory elements among chordates[2] "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 [3] "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[4]"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[5]"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[1]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.


Proposed Hox protein classification.jpg
Proposed Hox protein classification[4]


Developmental patterning signal.


Hindbrain neural crest migration.jpg

Hindbrain neural crest migration and Hox expression pattern[6]

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.


  • 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.[7]

Links: Axial Skeleton Development


Limb patterning factors 08.jpg

Mouse Limb Patterning Fgf and Hox Expression[8]

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

Links: Limb Development


Signaling Pathway

Additional Images


  1. 1.0 1.1 <pubmed>20485555</pubmed>| PLoS One
  2. <pubmed>22085760</pubmed>
  3. 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
  4. 4.0 4.1 <pubmed>20520839</pubmed>| PLoS One
  5. <pubmed>20540809</pubmed>| Reprod Biol Endocrinol.
  6. <pubmed>17948031</pubmed>
  7. <pubmed>20956304</pubmed>| Proc Natl Acad Sci U S A.
  8. <pubmed>20386744</pubmed>| PMC2851570 | PLoS Genet.


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


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

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Cite this page: Hill, M.A. (2021, March 9) Embryology Developmental Signals - Homeobox. Retrieved from

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© Dr Mark Hill 2021, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G