Connexins development

Fishman GI, Hertzberg EL, Spray DC, Leinwand LA Expression of connexin 43 in the developing rat heart. Circ Res 1991b 68 782-787. 

Gourdie RG, Green CR, Severs NJ, Thompson RP Immunolabelling patterns of gap junction connexins in the developing and mature rat heart. Anat Embryol (Berl) 1992 185 363-378. 

Veenstra RD, Berg K, Wang HZ, Westphale EM, Beyer EC Molecular and biophysical properties of the connexins from developing chick heart in Hah JE, Zampighi GA, Davis RM (eds) Gap Junctions. Progress in Cell Research, vol 3. Amsterdam, Elsevier, 1993, pp 89-95. 

Veenstra RD, Wang HZ, Westphale EM, Beyer EC Multiple connexins confer distinct regulatory and conductance properties of gap junctions in developing heart. Circ Res 1992 71 1277-1283. 

Connexins are tetra-pass membrane proteins that oligomerize into hexameric hemichannels called connnexons. These gap junction proteins are encoded by a multigene family. The presence of gap junctions and the expression of connexins has been described in many areas of the developing and adult central nervous system. Up to now, only connexin (Cx) 36 and Cx45 have been found to be expressed in neurons, besides Cx43 which is expressed in the olfactory epithelium. 

Investigations using these mice have shown that inactivation of certain connexin genes leads to the death of the embryo or fetus before birth. When other connexin genes are knocked out, embryonic and fetal development occur normally but, shortly after birth, the mice die because of defects in the organs in which the knocked-out connexins should have been expressed. Finally, when yet other connexin genes are knocked out, the mice survive to adulthood but then develop diseases such as peripheral neuropathy, liver cancer, and cataracts. 

The two-color pulse chase was developed to examine the turnover of gap junctions in HeLa cells [11]. Gap junctions are channels that connect adjacent cells and are permeable to small molecules and ions. They are composed of connexins, a family of transmembrane proteins with molecular weights ranging from 25 to 50 kDa. A functional channel is composed of 12 connexin subunits with each adjacent cell contributing a hexameric hemichannel. 

Development of a Reconstitution System for Study of Channels Formed by Connexin-32... 

It is hoped that such studies of single hemichannels will be complemented by studies of reconstituted junctional channels the double-membrane form. Development of a stable, well-characterized, and well-controlled double-membrane system is a challenging prospect. The literature on osmotic control of fusion of apposed bulged bilayers may be helpful in this regard (120, 121). Such a system would permit exploration of the forces involved in the assembly of junctional channels, which would be of interest from biophysical and cellular perspectives. For example, does the space between two membranes need to be dehydrated for hemichannels to interact (122) Do the hemichannels find each other by random interactions or does dielectric attraction (123-125) play a role Once junctional channels are formed, how reversible is the interaction between them and what forces tend to stabilize it Most important, how are the permeability, gating, and modulation of single hemichannels altered by interactions with each other in the doublemembrane form These and other considerations make the exploration of connexin channels in reconstituted systems of profound interest and promising prospects. 

Lefebvre DL, Piersanti M, Bai XH, Chen ZQ, Lye SJ (1995) Myometrial transcriptional regulation of the gap junction gene, Connexin-43. Reprod Fert Develop 7 603-611... 

Keywords connexin, heart development, cardiomyocyte, congenital heart disease, gap junction channel, gene delivery, peptidomimetics... 

Fig. 3. Early cardiac connexin Cx36.7 and its role in heart development. In the developing cardiomyocyte, zfCx36.7 forms a hexameric connexon on the plasma membrane. However, mutant zfCx36.7 cannot reach to the plasma membrane and are responsible forftk phenotype. Normal zfCx36.7 allows some small molecule/s to get into the cell and establishing the Nkx2.5 expression. Nkx2.5 in turn activates multiple genes related to heart development. The sequences of the activities...

S.R. Coppen, R.A. Kaba, D. Halliday, E. Dupont, J.N. Skepper, S. Elneil, N.J. Severs, Comparison of connexin expression patterns in the developing mouse heart and human foetal heart, Mol Cell Biochem 242 (2003) 121-127. 

L. Miquerol, L. Dupays, M. Theveniau-Ruissy, S. Alcolea, T. Jarry-Guichard, P. Abran, D. Gros, Gap junctional connexins in the developing mouse cardiac conduction system, Novartis Found Symp 250 (2003) 80-98 discussion 98-109, 276-109. 

R.J. Francis, C.W. Lo, Primordial germ cell deficiency in the connexin 43 knockout mouse arises from apoptosis associated with abnormal p53 activation. Development 133 (2006) 3451-3460. 

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