Abstract
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.
Highlights
In metazoans the Hox family of transcription factors (TFs) play important roles in patterning antero-posterior (A-P) identity along the body axis [1,2,3,4,5,6,7,8,9,10]
Schematic a model forfor thethe evolution tion of the vertebrate hindbrain based on comparative evolutionary analyses of key components of the axial patternof the vertebrate hindbrain gene regulatory network (GRN) based on comparative evolutionary analyses of key components of the axial patterning ing in deuterostomes, in relation to major events of genome rearrangement
A-P patterning system in chordates, and the high degree of conservation of aspects of the hindbrain GRN in vertebrates, it is interesting to question (1) when the retinoic acid (RA)/Hox regulatory hierarchy emerged during the course of evolution and (2) when this RA/Hox hierarchy become integrated into the GRN underlying hindbrain segmentation
Summary
In metazoans the Hox family of transcription factors (TFs) play important roles in patterning antero-posterior (A-P) identity along the body axis [1,2,3,4,5,6,7,8,9,10]. Genes in the Hox paralog groups (Hox PG1–PG4) are coupled to the process of segmentation and display segmentally restricted domains of expression, resulting in a ‘hindbrain Hox code’ [36,37,115,117,149,153,154,155,156,157,158,159,160,161,162,163,164,165,166] This code confers each rhombomere with a unique molecular identity that regulates programs of neurogenesis and elaboration of the neural circuitry associated with its distinct functions in the hindbrain [42,43,47,49,58,132–. We summarize how an RA morphogen gradient is set up in the developing hindbrain through a balance between synthesis and degradation and discuss the connection between the evolution of the RA signaling pathway and the hindbrain GRN in relation to diversity
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