Genetics of scapula and pelvis development: An evolutionary perspective

Abstract

In tetrapods, the scapular and pelvic girdles perform the important function of anchoring the limbs to the trunk of the body and facilitating the movement of each appendage. This shared function, however, is one of relatively few similarities between the scapula and pelvis, which have significantly different morphologies, evolutionary histories, embryonic origins, and underlying genetic pathways. The scapula evolved in jawless fish prior to the pelvis, and its embryonic development is unique among bones in that it is derived from multiple progenitor cell populations, including the dermomyotome, somatopleure, and neural crest. Conversely, the pelvis evolved several million years later in jawed fish, and it develops from an embryonic somatopleuric cell population. The genetic networks controlling the formation of the pelvis and scapula also share similarities and differences, with a number of genes shaping only one or the other, while other gene products such as PBX transcription factors act as hierarchical developmental regulators of both girdle structures. Here, we provide a detailed review of the cellular processes and genetic networks underlying pelvis and scapula formation in tetrapods, while also highlighting unanswered questions about girdle evolution and development.

Variation in mouse pelvic morphology maps to locations enriched in Sox9 Class II and Pitx1 regulatory features

“…In the QTL identified in the F 34 analysis and the QTL from the combined F 2 /F 34 analysis, we found there was a modest representation of genes with known roles in pelvic or bone development, as assessed by intersections with databases on gene expression and function (Table 4 and Table S2). Interestingly, many of the genes implicated as having core roles in the early patterning of the pelvic girdle, which include genes known to affect the patterning of the pelvis (Young et al, 2019) including the ilium ( Tbx4, Emx2, Fgf10 , and Pbx1 / 2 ), the pubis ( Alx1 / 4, Prrx1 , and Twist1 ), and possibly the ischium ( Pax1 ) were absent from QTL. However, residing within these intervals are two factors playing notable roles throughout pelvic development particularly at mesenchymal condensation and chondrogenesis stages.…”

“…Moreover, not all developmental pathways involved in the development of the pelvic girdle appear to channel the genetic influence responsible for generating individual differences in this population. This conclusion, however, is tempered by our relative dearth of knowledge on the developmental genetic mechanisms governing the pelvis, as compared with the limb for example (Sears et al, 2015; Young et al, 2019). Thus, knock‐out and other experiments using pelvic gene mutations of large effect may not afford clear insight into the mechanisms that can vary in natural populations.…”

“…This may arise from a partial separation between the action of gene regulatory networks and other developmental pathways responsible for laying out the basic patterning of a developing structure and those influencing variation through growth among nonpathological adults. Of a set of genes identified as playing a crucial role in the patterning of the mouse pelvic girdle by Young et al (2019), Sears et al (2015), and others (Capellini et al, 2006, 2011; Itou et al, 2012; Lanctôt et al, 1999; Marcil et al, 2003; Selleri et al, 2001), including Emx2, Fgf10, Pbx1 / 2, Pitx1, Sox9 , and Tbx4 in ilium patterning; Alx1 / 3 / 4, Islet1, Prrx1 , and Twist1 in pubis patterning; Pax1 and Islet1 in ischium patterning; only Sox9 was included in a QTL identified in the F 34 ‐only analysis while Pitx1 was found using additional results from the F 2 . These results are contingent, in part, on the particulars of the population in which we mapped the QTL.…”

“…After cell fate specification, the action of other transcription factors, such as Sox9 (Bi et al, 2001) and Emx2 (Malashichev, Borkhvardt, Christ, & Scaal, 2005; Malashichev, Christ, & Pröls, 2008; Pellegrini, Pantano, Fumi, Lucchini, & Forabosco, 2001), in cartilaginous anlagen then lead to cellular differentiation and the onset of endochondral ossification. Numerous signaling molecules interacting between the somatopleure, mesenchymal condensations, and surrounding tissues aid in the development and maturation of the ilium, ischium, and pubis (Young et al, 2019). While these studies provide vitally important insights into the genes and/or regulatory sequences involved in pelvic development, they do not provide an account of how developmental structures inherit phenotypic variation in pelvic form.…”

“…Most recently, these genetic approaches have been supplemented by studies in developmental biology with the aim of identifying the epigenetic processes involved in the specification, differentiation, and growth of the pelvic girdle (Capellini et al, 2011). Developmental investigations into pelvic form have given new insights into the mechanistic basis for the specification and differentiation of the hip bone (i.e., os coxa) and the adjacent, articulated sacrum (Sears, Capellini, & Diogo, 2015;Young, Selleri, & Capellini, 2019). Together, they show three of the pelvis' constituent elements (other than the sacrum), a cranially positioned ilium, a caudally/dorsally positioned ischium, and a ventrally located pubis, are specified early in embryonic development via the actions of key transcription factors, including Pitx1 (Lanctôt, Moreau, Chamberland, Tremblay, & Drouin, 1999;Marcil, Dumontier, Chamberland, Camper, & Drouin, 2003), Pbx1-3 (Capellini et al, 2006(Capellini et al, , 2011Selleri et al, 2001), and Islet1 (Itou et al, 2012), which partition the cells of the early somatopleuric field into distinct cranial and caudal domains.…”