Regulation of limb bud initiation and limb-type morphology. 2011

Veronique Duboc, and Malcolm P O Logan
Division of Developmental Biology, MRC-National Institute for Medical Research, London, UK.

While the paired forelimb and hindlimb buds of vertebrates are initially morphologically homogeneous, as the limb progenitors differentiate, each individual tissue element attains a characteristic limb-type morphology that ultimately defines the constitution of the forelimb or hindlimb. This review focuses on contemporary understanding of the regulation of limb bud initiation and formation of limb-type specific morphologies and how these regulatory mechanisms evolved in vertebrates. We also attempt to clarify the definition of the terms limb-type identity and limb-type morphology that have frequently been used interchangeably. Over the last decade, three genes, Tbx4, Tbx5, and Pitx1, have been extensively studied for their roles in limb initiation and determining limb-type morphologies. The role of Tbx4 and Tbx5 in limb initiation is clearly established. However, their putative role in the generation of limb-type morphologies remains controversial. In contrast, all evidence supports a function for Pitx1 in determination of hindlimb morphologies.

UI MeSH Term Description Entries
D009024 Morphogenesis The development of anatomical structures to create the form of a single- or multi-cell organism. Morphogenesis provides form changes of a part, parts, or the whole organism.
D005121 Extremities The farthest or outermost projections of the body, such as the HAND and FOOT. Limbs,Extremity,Limb
D005346 Fibroblast Growth Factors A family of small polypeptide growth factors that share several common features including a strong affinity for HEPARIN, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family. DNA Synthesis Factor,Fibroblast Growth Factor,Fibroblast Growth Regulatory Factor,Growth Factor, Fibroblast,Growth Factors, Fibroblast
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D018507 Gene Expression Regulation, Developmental Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism. Developmental Gene Expression Regulation,Embryologic Gene Expression Regulation,Gene Expression Regulation, Embryologic,Regulation of Gene Expression, Developmental,Regulation of Gene Expression, Embryologic,Regulation, Gene Expression, Developmental,Regulation, Gene Expression, Embryologic
D018878 Limb Buds Distinct regions of mesenchymal outgrowth at both flanks of an embryo during the SOMITE period. Limb buds, covered by ECTODERM, give rise to forelimb, hindlimb, and eventual functional limb structures. Limb bud cultures are used to study CELL DIFFERENTIATION; ORGANOGENESIS; and MORPHOGENESIS. Limb Bud,Bud, Limb,Buds, Limb
D020825 T-Box Domain Proteins Proteins containing a region of conserved sequence, about 200 amino acids long, which encodes a particular sequence specific DNA binding domain (the T-box domain). These proteins are transcription factors that control developmental pathways. The prototype of this family is the mouse Brachyury (or T) gene product. Proteins, T-Box Domain,T Box Domain Proteins

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