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Neural crest cells (NCCs) give rise to various tissues including neurons, pigment cells, bone and cartilage in the head.  Distal-less homeobox 5  ( Dlx5 ) is involved in both jaw patterning and differentiation of NCC-derivatives. In this study, we investigated the differentiation potential of head mesenchyme by forcing  Dlx5  to be expressed in mouse NCC ( NCC   Dlx5  ). In  NCC   Dlx5   mice, differentiation of dermis and pigment cells were enhanced with ectopic cartilage (ec) and heterotopic bone (hb) in different layers at the cranial vertex. The ec and hb were derived from the early migrating mesenchyme (EMM), the non-skeletogenic cell population located above skeletogenic supraorbital mesenchyme (SOM). The ec developed within  Foxc1  + -dura mater with increased PDGFRα signalling, and the hb formed with upregulation of BMP and WNT/β-catenin signallings in  Dermo1  + -dermal layer from E11.5. Since dermal cells express  Runx2  and  Msx2  in the control, osteogenic potential in dermal cells seemed to be inhibited by an anti-osteogenic function of  Msx2  in normal context. We propose that, after the non-skeletogenic commitment, the EMM is divided into dermis and meninges by E11.5 in normal development. Two distinct responses of the EMM, chondrogenesis and osteogenesis, to  Dlx5 -augmentation in the  NCC   Dlx5   strongly support this idea.

Dlx5-augmentation in neural crest cells reveals early development and differentiation potential of mouse apical head mesenchyme