As a developmental biology laboratory, we strive to understand the mechanisms by which cells acquire positional identity within embryonic tissue and thereby develop into a specific part of an organ. In particular, we are investigating the molecular genetic mechanisms behind craniofacial morphogenesis with emphasis on transcriptional regulation. Our laboratory utilizes multidisciplinary approaches including mouse genetics, genomics, biochemistry and molecular biology.

The current focus of research is development of the calvaria (upper part of the skull). The calvaria comprises plates of bone and fibrous joints (sutures and fontanels), and the balance between the two components is crucial. A perturbation in this balance can lead to craniosynostosis (premature loss of suture(s)), a major type of birth defects in humans. It occurs at a frequency of 1/2000 births, and it can leads to a dysmorphic skull that can further affect brain and orofacial development. The goal of our research is to provide detailed information on the genetic regulation of calvarial development, which will help us better understand related birth defects such as craniosynostosis.


Figure: Normal organization of the calvaria in newborn mouse

We have discovered that Lmx1b (LIM homeobox transcription factor 1b) gene plays a crucial role in normal development of the calvaria by preventing excess bone formation and loss of soft tissue joints. We are working to identify Lmx1b-downstream genetic network that regulates calvarial patterning. Also, we are trying to identify other genes that are important to this process.


Figure: Mouse Lmx1b mutants exhibit abnormal shape of the head and obliteration of multiple sutures at birth (Cesario et al., 2018 Dev Biol)