Coupling the roles of Hox genes to regulatory networks patterning cranial neural crest

Abstract

The neural crest is a transient population of cells that forms within the developing central nervous system and migrates away to generate a wide range of derivatives throughout the body during vertebrate embryogenesis. These cells are of evolutionary and clinical interest, constituting a key defining trait in the evolution of vertebrates and alterations in their development are implicated in a high proportion of birth defects and craniofacial abnormalities. In the hindbrain and the adjacent cranial neural crest cells (cNCCs), nested domains of Hox gene expression provide a combinatorial'Hox-code' for specifying regional properties in the developing head. Hox genes have been shown to play important roles at multiple stages in cNCC development, including specification, migration, and differentiation. However, relatively little is known about the underlying gene-regulatory mechanisms involved, both upstream and downstream of Hox genes. Furthermore, it is still an open question as to how the genes of the neural crest GRN are linked to Hox-dependent pathways. In this review, we describe Hox gene expression, function and regulation in cNCCs with a view to integrating these genes within the emerging gene regulatory network for cNCC development. We highlight early roles for Hox1 genes in cNCC specification, proposing that this may be achieved, in part, by regulation of the balance between pluripotency and differentiation in precursor cells within the neuro-epithelium. We then describe what is known about the regulation of Hox gene expression in cNCCs and discuss this from the perspective of early vertebrate evolution.

‘Building a perfect body’: control of vertebrate organogenesis by PBX-dependent regulatory networks

“…However, it remains challenging to envisage how factors such as PBX proteins with widespread presence can confer functional specificity to HOX proteins, which exhibit domain-restricted localization in vivo. Of note, recent studies have demonstrated that HOX proteins do in fact bind specific sequences in vivo and drive the expression of different target genes at different times in different tissues, thus executing distinct developmental programs (Alexander et al 2009;Crocker et al 2015;Beccari et al 2016;Sheth et al 2016;Jerkovic et al 2017;Parker et al 2018).…”

“…In the vertebrate embryo, the HB is transiently subdivided into distinct units called rhombomeres (Rs) and lateral outpocketings that form the brachial arches (BAs), which are populated by migrating neural crest cells (NCCs) ( Fig. 1; Parker et al 2018). Unique combinations of HOX proteins confer segmental identity along the HB (Fig.…”

HOXA10 induces BCL2 expression, inhibits apoptosis, and promotes cell proliferation in gastric cancer

“…Homeobox or HOX genes encode conserved transcription factors that regulate anterior‐posterior (A‐P) developing pattern and have been elaborated in detail over the last decade for their roles in the mechanisms underlying embryonic development . Recently, increasing evidence indicates that dysregulation of HOX family members maybe appear critical for the promotion of carcinogenesis .…”

“…Homeobox or HOX genes encode conserved transcription factors that regulate anterior-posterior (A-P) developing pattern and have been elaborated in detail over the last decade for their roles in the mechanisms underlying embryonic development. 3 Recently, increasing evidence indicates that dysregulation of HOX family members maybe appear critical for the promotion of carcinogenesis. [4][5][6] Preciously, we performed cDNA microarray and validated several differentially expressed HOX genes in GC-especially HOXA1, HOXA10, and HOXA13-with significantly higher expression in the cancerous tissues.…”

An atlas of anteriorhoxgene expression in the embryonic sea lamprey head:hox-code evolution in vertebrates

“…PA2 is homologous to the hyoid arch of gnathostomes, forming the velar support cartilage, while PA3-8 hold gills, like the posterior pharyngeal arches in aquatic gnathostomes. In gnathostomes, Hox PG2-4 genes have nested expression in pharyngeal arch NC that is broadly conserved between species, but paralogues often exhibit differences in expression levels (Parker et al, 2018). Previous studies in lamprey found conservation of select Hox domains in NC populations between lamprey and gnathostomes (Takio et al, 2007; Takio et al, 2004).…”