title: Tbx5 and Tbx4 are not sufficient to determine limb-specific morphologies but have common roles in initiating limb outgrowth.
abstract: Morphological differences between forelimbs and hindlimbs are thought to be regulated by Tbx5 expressed in the forelimb and Tbx4 and Pitx1 expressed in the hindlimb. Gene deletion and misexpression experiments have suggested that these factors have two distinct functions during limb development: the initiation and/or maintenance of limb outgrowth and the specification of limb-specific morphologies. Using genetic methods in the mouse, we have investigated the roles of Tbx5, Tbx4, and Pitx1 in both processes. Our results support a role for Tbx5 and Tbx4, but not for Pitx1, in initiation of limb outgrowth. In contrast to conclusions from gene misexpression experiments in the chick, our results demonstrate that Tbx5 and Tbx4 do not determine limb-specific morphologies. However, our results support a role for Pitx1 in the specification of hindlimb-specific morphology. We propose a model in which positional codes, such as Pitx1 and Hox genes in the lateral plate mesoderm, dictate limb-specific morphologies.
authors.affiliation: Division of Developmental Biology, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom.
authors.forename: Carolina
authors.initials: C
authors.lastname: Minguillon
authors.forename: Jo
authors.initials: J
authors.lastname: Del Buono
authors.forename: Malcolm P
authors.initials: MP
authors.lastname: Logan
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D019521:Body Patterning / Q000502:physiology; D001842:Bone and Bones / Q000196:embryology / Q000378:metabolism; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000502:physiology*; D005121:Extremities / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology; D017403:In Situ Hybridization / Q000379:methods; D018878:Limb Buds / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009024:Morphogenesis / Q000502:physiology*; D051761:Paired Box Transcription Factors; D020825:T-Box Domain Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology
chemical_list: D018398:Homeodomain Proteins; C490904:Hoxc4 protein, mouse; D051761:Paired Box Transcription Factors; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; C103177:Tbx4 protein, mouse; D014157:Transcription Factors; C101485:homeobox protein PITX1