Transcriptional control of axonal guidance and sorting in dorsal interneurons by the Lim-HD proteins Lhx9 and Lhx1

Antona

et al. 2014

Gene

Microdeletions of 17q12 including the hepatocyte nuclear factor 1 beta (HNF1B) gene, as well as point mutations of this gene, are associated with the Renal Cysts and Diabetes syndrome (RCAD, OMIM 137920) and genitourinary alterations. Also, microdeletions encompassing HNF1B were identified as a cause of Mayer-RokitanskyKüster-Hauser Syndrome (MRKH, OMIM 277000) in females and, recently, were associated with intellectual disability, autistic features, cerebral anomaly and facial dysmorphisms. In this report, we describe a boy with a deletion in 17q12 region detected by SNP array, encompassing the HNF1B gene, that showed dysmorphic features, intellectual disability (ID), serious speech delay and autistic features. In addition, obesity was observed. In order to study the parental origin of the rearrangement, we analyzed selected SNPs in the deleted area in the patient and his parents, showing Mendelian incompatibilities suggesting a de novo deletion on the chromosome of maternal origin. Our case confirms the incomplete penetrance and variable expressivity of this deletion, its complex clinical variability, and strengthens the evidence that ID and stereotyped behaviors may be part of the phenotypic spectrum characterizing the affected patients. Also, it is useful to further delineate the phenotypes associated to the deletion being the first case in which obesity has been documented. We present a genotype-phenotype correlation discussing the possible role of some genes, encompassed by the deletion, in the etiology of the observed phenotypes.

Section: Discussionmentioning

confidence: 99%

Variable phenotype in 17q12 microdeletions: Clinical and molecular characterization of a new case

Antona

et al. 2014

Gene

Proc. Natl. Acad. Sci. U.S.A.

“…2F. This approach enabled stable lineage tracing of the enhancer expressing cells (8,24,25). Six hours after ventral to dorsal electroporation of NTs, GFP + cells were restricted to the dorsal NT, where cells expressing endogenous Foxd3 are located (8).…”

Section: Resultsmentioning

confidence: 99%

“…A plasmid containing the #168 enhancer from the Vista enhancer browser (http:// enhancer.lbl.gov) driving expression of Cre recombinase was coelectroporated into dorsal NT along with a reporter plasmid in which a floxed transcriptional STOP module was inserted between the CAGG enhancer/promoter and the GFP gene (pCAGG::LoxP-STOP-LoxP-GFP) (25,33).…”

Section: Methodsmentioning

confidence: 99%

Neural crest and Schwann cell progenitor-derived melanocytes are two spatially segregated populations similarly regulated by Foxd3

Nitzan

Pfaltzgraff

Labosky

et al. 2013

103

Skin melanocytes arise from two sources: either directly from neural crest progenitors or indirectly from neural crest-derived Schwann cell precursors after colonization of peripheral nerves. The relationship between these two melanocyte populations and the factors controlling their specification remains poorly understood. Direct lineage tracing reveals that neural crest and Schwann cell progenitor-derived melanocytes are differentially restricted to the epaxial and hypaxial body domains, respectively. Furthermore, although both populations are initially part of the Foxd3 lineage, hypaxial melanocytes lose Foxd3 at late stages upon separation from the nerve, whereas we recently found that epaxial melanocytes segregate earlier from Foxd3-positive neural progenitors while still residing in the dorsal neural tube. Gain-and loss-offunction experiments in avians and mice, respectively, reveal that Foxd3 is both sufficient and necessary for regulating the balance between melanocyte and Schwann cell development. In addition, Foxd3 is also sufficient to regulate the switch between neuronal and glial fates in sensory ganglia. Together, we propose that differential fate acquisition of neural crest-derived cells depends on their progressive segregation from the Foxd3-positive lineage.

“…To specifically label these axons, an enhancer element (Atoh1), that has previously been characterized as specific for spinal dI1 neurons 8,12,13 , was confirmed to be expressed in hindbrain dA1 cells 10 . The element was cloned upstream to Cre recombinase and co-electroporated at E2.75 along with a Cre dependent cytoplasmic GFP reporter plasmid (pCAGG-LoxP-Stop-LoxP-cGFP; Figure 1BI).…”

Section: Representative Resultsmentioning

confidence: 99%

“…We have previously utilized specific enhancer elements, and a Cre/ LoxP-based conditional expression system for tracking axonal trajectory of dorsal spinal interneurons in the early chick embryo [7][8][9] . In the current manuscript we have targeted the hindbrain and upgraded the experimental paradigm for labeling late embryonic hindbrain interneurons, axons and their synaptic targets, using a modified electroporation strategy and the PiggyBac -mediated DNA transposition.…”

Section: Introductionmentioning

confidence: 99%

Electroporation of the Hindbrain to Trace Axonal Trajectories and Synaptic Targets in the Chick Embryo

Kohl

Hadas

Klar

et al. 2013

JoVE

Self Cite

Electroporation of the chick embryonic neural tube has many advantages such as being quick and efficient for the expression of foreign genes into neuronal cells. In this manuscript we provide a method that demonstrates uniquely how to electroporate DNA into the avian hindbrain at E2.75 in order to specifically label a subset of neuronal progenitors, and how to follow their axonal projections and synaptic targets at much advanced stages of development, up to E14.5. We have utilized novel genetic tools including specific enhancer elements, Cre/Loxbased plasmids and the PiggyBac-mediated DNA transposition system to drive GFP expression in a subtype of hindbrain cells (the dorsal most subgroup of interneurons, dA1). Axonal trajectories and targets of dA1 axons are followed at early and late embryonic stages at various brainstem regions. This strategy contributes advanced techniques for targeting cells of interest in the embryonic hindbrain and for tracing circuit formation at multiple stages of development. Video LinkThe video component of this article can be found at