Cell Recognition and Synapse Formation

Nirenberg, M.

Abstract

Approximately 3.5 kb of the 5'-upstream region of the Drosophila NK-2 homeobox gene was sequenced and putative binding sites were found for proteins that regulate gene expression. The first expression of the NK-2 gene coincides in time and place with the appearance of the neurogenic anlage, which suggests that NK-2 homeobox protein functions as an activator of the gene program that leads to the formation of part of the brain, subesophageal ganglion, and ventral nerve cord. Expression of the NK-1 homeobox gene is initiated 6 hr after fertilization in ganglion mother cells that give rise to a subset of neurons in the CNS and in a subset of founder muscle cell. Many transgenic Drosophila lines were generated by transposition of a P element that contains a beta- galactosidase gene that express beta-galactosidase during embryonic development only in the nervous system. Two novel mouse homeobox cDNAs were cloned (Hox 1.11 and CL-125). Hox 1.11 cDNA encodes a protein with a homeodomain similar to that of Hox 2.8 and an acidic domain. The Hox 1.11 gene was mapped to mouse chromosome 6. CL-125 cDNA encodes a protein with a homeodomain related to that of Hox 1.6. Two novel species of mouse Pou-box-homeobox DNA were cloned (C-1 and G-1). The C-1 gene is expressed only in adult brain and salivary glands. Neuroblastoma or hybrid cell lines were found that express brain-specific species of C-1 mRNA. Mouse genomic DNA fragments that activate replication of an E. coli-mammalian cell shuttle vector were selectively amplified and cloned. Some of the DNA clones contain novel enhancer or promoter sequences. The 5'-upstream region of a novel voltage-sensitive calcium channel alpha1- subunit gene from rat brain was cloned and sequenced. Expression of this calcium channel gene in NG108-15 cells was dependent upon elevation of cellular cAMP for several days. Fragments of DNA from the 5' upstream region of the calcium channel gene activate transcription of a reporter gene. The cAMP-dependent regulation of calcium channel mRNA ultimately regulates the efficiency of transynaptic communication.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Heart, Lung, and Blood Institute (NHLBI)
• Type: Intramural Research (Z01)
• Project #: 1Z01HL000009-17
• Application #: 3857949
• Support Year: 17
• Fiscal Year: 1991

Institution

• Name: National Heart, Lung, and Blood Institute
• Country: United States

Publications

Xia, Menghang; Huang, Ruili; Guo, Vicky et al. (2009) Identification of compounds that potentiate CREB signaling as possible enhancers of long-term memory. Proc Natl Acad Sci U S A 106:2412-7

Sharma, Shail K; Nirenberg, Marshall (2007) Silencing of genes in cultured Drosophila neurons by RNA interference. Proc Natl Acad Sci U S A 104:12925-30

Koizumi, Keita; Higashida, Haruhiro; Yoo, Siuk et al. (2007) RNA interference screen to identify genes required for Drosophila embryonic nervous system development. Proc Natl Acad Sci U S A 104:5626-31

Chen, Xiaobing; Vinade, Lucia; Leapman, Richard D et al. (2005) Mass of the postsynaptic density and enumeration of three key molecules. Proc Natl Acad Sci U S A 102:11551-6

Ivanov, Andrej I; Rovescalli, Alessandra C; Pozzi, Paola et al. (2004) Genes required for Drosophila nervous system development identified by RNA interference. Proc Natl Acad Sci U S A 101:16216-21

Lum, Lawrence; Yao, Shenqin; Mozer, Brian et al. (2003) Identification of Hedgehog pathway components by RNAi in Drosophila cultured cells. Science 299:2039-45

Nirenberg, Marshall (2003) The genetic revolution: the importance of flies and worms. Am J Psychiatry 160:615

Koizumi, Keita; Lintas, Carla; Nirenberg, Marshall et al. (2003) Mutations that affect the ability of the vnd/NK-2 homeoprotein to regulate gene expression: transgenic alterations and tertiary structure. Proc Natl Acad Sci U S A 100:3119-24

Hwang, Kae-Jung; Xiang, Bosong; Gruschus, James M et al. (2003) Distortion of the three-dimensional structure of the vnd/NK-2 homeodomain bound to DNA induced by an embryonically lethal A35T point mutation. Biochemistry 42:12522-31

Wang, Lan-Hsiang; Chmelik, Rebecca; Nirenberg, Marshall (2002) Sequence-specific DNA binding by the vnd/NK-2 homeodomain of Drosophila. Proc Natl Acad Sci U S A 99:12721-6