Annual Report 2011 - Center for Advanced Biotechnology and ...

More documents

Recommendations

Info

Dr. Mengqing Xiang CABM Resident Faculty Member Professor Department of Pediatrics UMDNJ-Robert Wood Johnson Medical School Dr. Kangxin Jin Postdoctoral Associate Dr. Shengguo Li Research Teaching Spec. Dr. Huijun Luo Research Teaching Spec. Dr. Kamana Misra Research Teaching Spec. Min Zou Graduate Student Molecular Neurodevelopment Laboratory Dr. Mengqing Xiang came to CABM in September 1996 from the Johns Hopkins University School of Medicine where he conducted postdoctoral studies with Dr. Jeremy Nathans. He earned his Ph.D. at the University of Texas M.D. Anderson Cancer Center and has received a number of honors including a China-U.S. Government Graduate Study Fellowship, a Howard Hughes Medical Institute Postdoctoral Fellowship, a Basil O’Connor Starter Scholar Research Award and a Sinsheimer Scholar Award. In 2003 he received the Award in Auditory Science from the National Organization for Hearing Research Foundation. His work is currently supported by NIH. Our laboratory investigates the molecular mechanisms that govern the determination and differentiation of the highly specialized sensory cells and neurons. We employ a variety of molecular genetic approaches to identify and study transcription and other regulatory factors that are required for programming development of the retina, inner ear, spinal cord, and other CNS areas. A major focus of our work is to develop animal models to study the roles of these regulatory genes during normal sensorineural development, as well as to elucidate how mutations in these genes cause sensorineural disorders such as blindness and deafness. Generation of a transgenic line for studying V2 neuronal lineages and functions in the spinal cord. During spinal neurogenesis, the p2 progenitor domain generates at least three subclasses of interneurons named V2a, V2b and V2c, which are crucial components of the locomotor central pattern generator. We have previously shown that the winged-helix/forkhead transcription factor Foxn4 is expressed in a subset of p2 progenitors and required for specifying V2b interneurons. To determine the cell lineages derived from Foxn4-expressing progenitors, we generated a Foxn4-Cre BAC transgenic mouse line that drives Cre recombinase expression, mimicking endogenous Foxn4 expression pattern in the developing spinal cord. We used this transgenic line to map neuronal lineages derived from Foxn4-expressing progenitors and found that they gave rise to all neurons of the V2a, V2b as well as the newly identified V2c lineages. These data suggest that Foxn4 may be transiently expressed by all p2 progenitors and that the Foxn4-Cre line may serve as a useful genetic tool not only for lineage analysis but also for functional studies of genes and neurons involved in locomotion. 35
Diverse developmental roles of Foxn4. In our previous studies, we have shown that Foxn4 is transiently expressed in a subset of progenitors during retinogenesis and spinal neurogenesis. Targeted inactivation and gain-of-function analyses have revealed an essential function of Foxn4 in the generation of amacrine and horizontal cells during retinal development as well as in specifying the V2b interneurons during spinal cord development. In collaboration with Drs. Stavros Malas (University of Cyprus) and William Richardson (University College London), we have now used genetic fate mapping and loss-of-function analysis to show that the transcription factor Sox1 is expressed in and required for a third type of p2-derived interneuron, which we named V2c. These are close relatives of V2b interneurons, and, in the absence of Sox1, they switch to the V2b fate. The absence of Foxn4 results in a complete loss of Sox1-expressing V2c neurons, indicating that Foxn4 is necessary for specifying not only V2b but also V2c interneuron subtypes. In another collaboration with Dr. Jeffrey Goldberg (University of Miami, Miller School of Medicine), we observed a developmental delay in the distribution of RGC (retinal ganglion cell) projections to the superior colliculus. Moreover, RGC axons failed to penetrate into the retinorecipient layers in Foxn4 mutant mice. Foxn4 was not expressed by RGCs and was undetectable in the superior colliculus itself. Thus, Foxn4 may be indirectly required for RGC distal axon patterning. Aside from its neural expression, we have also shown that during murine lung development Foxn4 is expressed in proximal airways by a subpopulation of postmitotic epithelial cells which are distinct from basal and ciliated cells. Foxn4 inactivation causes dilated alveoli, thinned alveolar walls and reduced septa in the distal lung but no overt gross alterations in proximal airways, suggesting that Foxn4 may have a non-cell-autonomous role critical for alveologenesis during lung development. Together, our data suggest that Foxn4 may play multiple cell-autonomous and non-cell-autonomous roles during epithelial cell development. Brn3a regulates dorsal root ganglion sensory neuron specification and axonal projection into the spinal cord. The sensory neurons of the dorsal root ganglia (DRG) must project accurately to their central targets to convey proprioceptive, nociceptive and mechanoreceptive information to the spinal cord. How these different sensory modalities and central connectivities are specified and coordinated still remains unclear. Given the expression of the POU homeodomain transcription factors Brn3a and Brn3b in DRG and spinal cord sensory neurons, we analyzed subtype specification of DRG and spinal cord sensory neurons as well as DRG central projections in Brn3a and Brn3b single and double mutant mice. Inactivation of either or both genes causes no gross abnormalities in early spinal cord neurogenesis; however, in Brn3a single and Brn3a;Brn3b double mutant mice, sensory afferent axons from the DRG fail to form normal trajectories in the spinal cord. The TrkA + cutaneous nociceptive afferents stay outside the dorsal horn and fail to extend into the spinal cord, while the projections of TrkC + proprioceptive afferents into the ventral horn are also impaired. Moreover, Brn3a mutant DRGs are defective in sensory neuron specification, as marked by the excessive generation of TrkB + and TrkC + neurons as well as TrkA + /TrkB + and TrkA + /TrkC + double positive cells at early embryonic stages. At later stages in the mutant, TrkB + , TrkC + and parvalbumin + 36
Page 1: CENTER FOR ADVANCED BIOTECHNOLOGY A
Page 4 and 5: Director’s Overview CABM—25 and
Page 6 and 7: of Health, National Science Foundat
Page 8 and 9: Cell & Developmental Biology Labora
Page 10 and 11: protein metabolism/activity, such t
Page 12 and 13: Dr. Céline Gélinas CABM Resident
Page 14 and 15: (CHINJ, CINJ and CABM) and Lauri Go
Page 16 and 17: Dr. Masayori Inouye CABM Resident F
Page 18 and 19: Xu, Z., Mirochnitchenko, O., Xu, C.
Page 20 and 21: Dr. Fang Liu CABM Resident Faculty
Page 22 and 23: Publications: Matsuura, I., Chiang,
Page 24 and 25: In the prior year, we have made con
Page 26 and 27: Dr. James Millonig CABM Resident Fa
Page 28 and 29: We have mapped 5 different vl modif
Page 30 and 31: Dr. Arnold Rabson Director Child He
Page 32 and 33: Publications: Zheng, X., Cui, X.X.,
Page 34 and 35: polymerase II, facilitating the sel
Page 38 and 39: neurons diminish while there is a s
Page 40 and 41: Laboratory Faculty Director Structu
Page 42 and 43: Human transcription factors are typ
Page 44 and 45: atomic detail and have yielded nume
Page 46 and 47: Figure from Das et al., 2011 showin
Page 48 and 49: Dr. Helen M. Berman Board of Govern
Page 50 and 51: Dr. Chenghua Shao Research Associat
Page 52 and 53: Dr. Joseph Marcotrigiano CABM Resid
Page 54 and 55: The long-term goals of our studies
Page 56 and 57: s Publications: Singarapu, K.K., Mi
Page 58 and 59: Zhao, L., Zhao, K., Hurst, R., Slat
Page 60 and 61: Acton, T.B., Xiao, R., Anderson, S.
Page 62 and 63: Kryshtafovych, A., Bartual, S.G., B
Page 64 and 65: properties by lowering susceptibili
Page 66 and 67: Dr. Ann M. Stock Associate Director
Page 68 and 69: Publications: Barbieri, C.M., Mack,
Page 70 and 71: Lectures and Seminars 69
Page 72 and 73: CABM RETREAT, June 30, 2011 Cook Ca
Page 75 and 76: 25 th Anniversary CABM Symposium Fr
Page 77 and 78: Edery Lab Joseph Albistur George Gh
Page 79 and 80: PATENTS P. Lobel, et al. “Methods
Page 81 and 82: Montelione, G.T., Ma, L. and Krug,
Page 83 and 84: Outside Academic Members Dr. Wayne
Page 85 and 86: Former CABM Scientific Advisory Boa
Page 87 and 88:
Fiscal Information 86
Page 89 and 90:
Anderson, Stephen Rutgers CABM Gran
Page 91 and 92:
Leukemia & Lymphoma Society BFL-1 a
Page 93 and 94:
Total Award Start - End FY 2011 Dir
Page 95 and 96:
Department of Defense Tumor suppres
Page 97 and 98:
Total Award Start - End FY 2011 Dir
show all

Annual Report 2011 - Center for Advanced Biotechnology and ...

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?