Abstract
Coordination of craniofacial development involves an complex, intricate, genetically controlled and tightly regulated spatiotemporal series of reciprocal inductive and responsive interactions among the embryonic cephalic epithelia (both endodermal and ectodermal) and the cephalic mesenchyme — particularly the cranial neural crest (CNC). The coordinated regulation of these interactions is critical both ontogenetically and evolutionarily, and the clinical importance and mechanistic sensitivity to perturbation of this developmental system is reflected by the fact that one-third of all human congenital malformations affect the head and face. Here, we focus on one element of this elaborate process, apoptotic cell death, and its role in normal and abnormal craniofacial development. We highlight four themes in the temporospatial elaboration of craniofacial apoptosis during development, namely its occurrence at (1) positions of epithelial-epithelial apposition, (2) within intra-epithelial morphogenesis, (3) during epithelial compartmentalization, and (4) with CNC metameric organization. Using the genetic perturbation of Satb2, Pbx1/2, Fgf8, and Foxg1 as exemplars, we examine the role of apoptosis in the elaboration of jaw modules, the evolution and elaboration of the lambdoidal junction, the developmental integration at the mandibular arch hinge, and the control of upper jaw identity, patterning and development. Lastly, we posit that apoptosis uniquely acts during craniofacial development to control patterning cues emanating from core organizing centres.
Highlights
Craniogenesis, the development of a patterned and functionally integrated head, is an especially elaborate process, one under intense developmental and evolutionary pressures (Gans and Northcutt, 1983; Depew and Simpson, 2006; Green et al, 2015; Marcucio et al, 2015)
As we present below, such topographies are exemplified by the appositions of the developing palatal shelves, the meeting of the FNP and mxBA1 at λ, the eyelids, the pharyngeal plate (PPt) and precervical sinus, and the buccopharyngeal membrane
We discuss (1) how the absence of Satb2 leads to increased apoptosis within the cranial neural crest (CNC) of the coordinated jaw developmental modules in which it is expressed, (2) the role of Pbx genes in controlling apoptosis in the nasal fin at λ and the plausible significance of this for craniofacial development (CFD) and evolution, (3) how attenuation of Fgf8 expression leads to increased apoptosis in the CNC at the hinge as well as decouples jaw integration, and (4) how loss of Foxg1 leads to drastically altered apoptotic topography in the surface cephalic ectoderm (SCE) and its signaling centres that results in the loss of suppression of lower jaw molecular identity in the upper jaw primordia
Summary
Craniogenesis, the development of a patterned and functionally integrated head, is an especially elaborate process, one under intense developmental and evolutionary pressures (Gans and Northcutt, 1983; Depew and Simpson, 2006; Green et al, 2015; Marcucio et al, 2015). In part because the trigeminal CNC are, initially at least, equipotent in their response to local patterning cues, among the fundamental tasks in patterning BA1 and the jaws are: (1) establishing upper jaw versus lower jaw positional identity within the CNC, (2) generating and maintaining the point of articulation between the upper and lower jaw arcades, and (3) keeping the arcades in appropriate functional registration during subsequent development and morphogenesis Actualization of these tasks involves elaboration of a “hinge and caps” system of establishing positional information in the CNC through several regional signaling centres (Depew et al, 2002a; Depew and Compagnucci, 2008; Compagnucci et al, 2013). In a topographically complex manner, the SCE of λ secretes a significant range of signaling molecules such that λ acts as the upper jaw “cap” organizing centre integrating mxBA1 development distal to the hinge region with that of the FNP This includes the structural integration of the premaxillae, maxillae, and nasal capsules. “morphogenic” apoptosis has been deemed a principal sculptor of embryonic structures during morphogenesis, organogenesis and remodelling - the holotype sculpture being the apoptotic elimination of cells in the inter-digital webbing of the developing amniote autopod (Glücksmann, 1951; Saunders, 1966; Hinchliffe, 1981)
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