Disruption of SATB2 or its long-range cis-regulation by SOX9 causes a syndromic form of Pierre Robin sequence.

Heterozygous loss-of-function (LOF) mutations in the gene encoding the DNA-binding protein, SATB2, result in micrognathia and cleft palate in both humans and mice. In three unrelated individuals, we show that translocation breakpoints (BPs) up to 896 kb 3' of SATB2 polyadenylation site cause a phenotype which is indistinguishable from that caused by SATB2 LOF mutations. This syndrome comprises long nose, small mouth, micrognathia, cleft palate, arachnodactyly and intellectual disability. These BPs map to a gene desert between PLCL1 and SATB2. We identified three putative cis-regulatory elements (CRE1-3) using a comparative genomic approach each of which would be placed in trans relative to SATB2 by all three BPs. CRE1-3 each bind p300 and mono-methylated H3K4 consistent with enhancer function. In silico analysis suggested that CRE1-3 contain one or more conserved SOX9-binding sites, and this binding was confirmed using chromatin immunoprecipitation on cells derived from mouse embryonic pharyngeal arch. Interphase bacterial artificial chromosome fluorescence in situ hybridization measurements in embryonic craniofacial tissues showed that the orthologous region in mice exhibits Satb2 expression-dependent chromatin decondensation consistent with Satb2 being a target gene of CRE1-3. To assess their in vivo function, we made multiple stable reporter transgenic lines for each enhancer in zebrafish. CRE2 was shown to drive SATB2-like expression in the embryonic craniofacial region. This expression could be eliminated by mutating the SOX9-binding site of CRE2. These observations suggest that SATB2 and SOX9 may be acting together via complex cis-regulation to coordinate the growth of the developing jaw.

Using co-teaching as a means of facilitating interprofessional collaboration in health and social care.

In this paper we report the findings of a collaborative enquiry on our experience as tutors co-teaching interprofessional collaboration to a multidisciplinary group of undergraduates. We have different professional/academic backgrounds and the student group included health and social work professionals alongside a number of non-professionals. Our data included our perceptions of the co-teaching experience collected by means of our reflective diaries and reflective conversations during planning and after teaching sessions. We also collected data on student perceptions elicited by means of student evaluations and a student focus group discussion. The data illuminate the process of using co-teaching to role model shared learning and collaborative working within the classroom and highlight the importance of carefully planning co-teaching interaction, including the use of humour, tension, different knowledge bases and styles of debate. The deliberate use of the interactions made possible by coteaching enabled us to create an active learning environment that facilitated the teaching of collaboration. Drawing on our experience, we discuss the considerable potential of using co-teaching to role model collaborative working for multidisciplinary student groups.