Null mutation of Dlx-2 results in abnormal morphogenesis of proximal first and second branchial arch derivatives and abnormal differentiation in the forebrain.

TLDR

Genetic analysis of vertebrate head development is at a primitive stage, and homeobox genes such as the Distal‑less family are potential regulators of head development. The study aimed to determine Dlx‑2 function by generating a null mutation in mice and hypothesized that first‑arch skull bones transform into reptile‑like structures. A null mutation of Dlx‑2 was created in mice via gene targeting. Homozygous mutants exhibit abnormal forebrain differentiation and respecification of cranial neural crest cells, causing abnormal morphogenesis of proximal first and second branchial arch skeletal elements, demonstrating that Dlx‑2 controls branchial arch and forebrain development and implicating it in craniofacial evolution.

Abstract

Genetic analysis of the development and evolution of the vertebrate head is at a primitive stage. Many homeo box genes, including the Distal-less family, are potential regulators of head development. To determine the function of Dlx-2, we generated a null mutation in mice using gene targeting. In homozygous mutants, differentiation within the forebrain is abnormal and the fate of a subset of cranial neural crest cells is respecified. The latter causes abnormal morphogenesis of the skeletal elements derived from the proximal parts of the first and second branchial arches. We hypothesize that the affected skull bones from the first arch have undergone a transformation into structures similar to those found in reptiles. These results show that Dlx-2 controls development of the branchial arches and the forebrain and suggests its role in craniofacial evolution.