Retinoic Acid Signaling in Vertebrate Hindbrain Segmentation: Evolution and Diversification

In metazoans, Hox genes are key drivers of morphogenesis. In chordates, they play important roles in patterning the antero-posterior (A-P) axis. A crucial aspect of their role in axial patterning is their collinear expression, a process thought to be linked to their response to major signaling pathways such as retinoic acid (RA) signaling. The amplification of Hox genes following major events of genome evolution can contribute to morphological diversity. In vertebrates, RA acts as a key regulator of the gene regulatory network (GRN) underlying hindbrain segmentation, which includes Hox genes. This review investigates how the RA signaling machinery has evolved and diversified and discusses its connection to the hindbrain GRN in relation to diversity. Using non-chordate and chordate deuterostome models, we explore aspects of ancient programs of axial patterning in an attempt to retrace the evolution of the vertebrate hindbrain GRN. In addition, we investigate how the RA signaling machinery has evolved in vertebrates and highlight key examples of regulatory diversification that may have influenced the GRN for hindbrain segmentation. Finally, we describe the value of using lamprey as a model for the early-diverged jawless vertebrate group, to investigate the elaboration of A-P patterning mechanisms in the vertebrate lineage.

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CDX4 regulates the progression of neural maturation in the spinal cord

10.1101/177469 ◽

2017 ◽

Author(s):

Piyush Joshi ◽

Andrew J. Darr ◽

Isaac Skromne

Keyword(s):

Spinal Cord ◽

Transcription Factors ◽

Retinoic Acid ◽

Gene Regulatory Network ◽

Neural Tube ◽

Regulatory Network ◽

Neural Differentiation ◽

Retinoic Acid Signaling ◽

Gene Regulatory ◽

Differentiation Marker

ABSTRACTThe progressive maturation of cells down differentiation lineages is controlled by collaborative interactions between networks of extracellular signals and intracellular transcription factors. In the vertebrate spinal cord, FGF, Wnt and Retinoic Acid signaling pathways regulate the progressive caudal-to-rostral maturation of neural progenitors by regulating a poorly understood gene regulatory network of transcription factors. We have mapped out this gene regulatory network in the chicken pre-neural tube, identifying CDX4 as a dual-function core component that simultaneously regulates gradual loss of cell potency and acquisition of differentiation states: in a caudal-to-rostral direction, CDX4 represses the early neural differentiation marker Nkx1.2 and promotes the late neural differentiation marker Pax6. Significantly, CDX4 prevents premature PAX6-dependent neural differentiation by blocking Ngn2 activation. This regulation of CDX4 over Pax6 is restricted to the rostral pre-neural tube by Retinoic Acid signaling. Together, our results show that in the spinal cord, CDX4 is part of the gene regulatory network controlling the sequential and progressive transition of states from high to low potency during neural progenitor maturation. Given CDX well-known involvement in Hox gene regulation, we propose that CDX factors coordinate the maturation and axial specification of neural progenitor cells during spinal cord development.

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Hox genes: Downstream “effectors” of retinoic acid signaling in vertebrate embryogenesis

genesis ◽

10.1002/dvg.23306 ◽

2019 ◽

pp. e23306 ◽

Cited By ~ 8

Author(s):

Christof Nolte ◽

Bony De Kumar ◽

Robb Krumlauf

Keyword(s):

Retinoic Acid ◽

Hox Genes ◽

Retinoic Acid Signaling ◽

Downstream Effectors

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Characterisation of the role and regulation of Ultrabithorax in sculpting fine-scale leg morphology

10.1101/2020.06.17.152918 ◽

2020 ◽

Author(s):

Alexandra D. Buffry ◽

Sebastian Kittelmann ◽

Alistair P. McGregor

Keyword(s):

Gene Regulatory Networks ◽

Regulatory Network ◽

Regulatory Networks ◽

Hox Genes ◽

Regional Identity ◽

Fine Scale ◽

Hox Gene ◽

Leg Development ◽

Gene Regulatory ◽

Leg Morphology

AbstractHox genes are expressed during embryogenesis and determine the regional identity of animal bodies along the antero-posterior axis. However, they also function post-embryonically to sculpt fine-scale morphology. To better understand how Hox genes are integrated into post-embryonic gene regulatory networks, we further analysed the role and regulation of Ultrabithorax (Ubx) during mesothoracic (T2) leg development in Drosophila melanogaster. Ubx represses leg trichomes in the proximal posterior region of the T2 femur (the so-called naked valley) and we found that it likely does so through activating the expression of microRNA-92a. We also identified a T2 leg enhancer of Ubx that recapitulates the temporal and regional activity of this Hox gene in these appendages. Analysis of motifs in this enhancer predicted that it is bound by Distal-less (Dll) and we found that knockdown of Dll results in the loss of trichomes on the T2 femur. This suggests that while Ubx activates microRNA-92a to repress trichomes in the naked valley region of the proximal femur, Dll may repress Ubx more distally to enable formation of trichomes. Taken together our results provide insights into how Ubx is integrated into a postembryonic gene regulatory network to determine fine-scale leg morphology.

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