RESUMO
In this perspective I look back on the twists and turns that influenced the direction of my scientific career over the past 40 years. From my early ambition to be a chemist to my training in Philadelphia and Bethesda as a molecular biologist, I benefited enormously from generous and valuable mentoring. In my independent career in Philadelphia and Princeton, I was motivated by a keen interest in the changes in gene expression that direct the development of the mammalian embryo and inspired by the creativity and energy of my students, fellows, and research staff. After twelve years as President of Princeton University, I have happily returned to the faculty of the Department of Molecular Biology.
Assuntos
Biologia Molecular/história , Universidades/história , Sequência de Aminoácidos , Animais , Canadá , Passeio de Cromossomo , Desenvolvimento Embrionário/genética , Proteínas do Olho/genética , Proteínas do Olho/história , Regulação da Expressão Gênica no Desenvolvimento , Impressão Genômica , História do Século XX , História do Século XXI , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/história , Humanos , Camundongos , Dados de Sequência Molecular , National Institutes of Health (U.S.) , New Jersey , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados/genética , Fatores de Transcrição Box Pareados/história , Splicing de RNA , RNA Longo não Codificante/genética , RNA Longo não Codificante/história , Proteínas Repressoras/genética , Proteínas Repressoras/história , Estados Unidos , alfa-Fetoproteínas/genética , alfa-Fetoproteínas/história , Globinas beta/genética , Globinas beta/históriaRESUMO
Already in 1981 Davis had reported that small Yp terminal deletion resulted in short stature and, basing his findings on Davis's results, on the results of other publications, and on his own observations that Xp terminal deletions normally result in short stature regardless of the breakpoints, in 1993 Ogata suggested that a growth gene was located in the pseudoautosomal region (PAR) and that haploinsufficiency of the growth gene actually caused short stature as a dominant phenotype. Rao et al. in 1997 cloned a gene from the distal part of the PAR and gave it the name SHOX for "short stature homeobox-containing" gene. SHOX is expressed from an inactive X chromosome and an active X and a normal Y chromosome, indicating that SHOX produces the dosage effect in sex chromosome aberrations. In the same year, both Ellison and Rao demonstrated that SHOX is most clearly expressed in bone marrow fibroblasts, thus suggesting that SHOX has a particular importance in bone growth and maturation.
Assuntos
Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/história , Desenvolvimento Ósseo/fisiologia , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Feminino , Deleção de Genes , História do Século XX , História do Século XXI , Proteínas de Homeodomínio/fisiologia , Humanos , Masculino , Proteína de Homoeobox de Baixa EstaturaRESUMO
In 1867 Alexander Kowalevsky published an account of the development of the cephalochordate Amphioxus lanceolatus (now known as Branchiostoma lanceolatum) (Kowalevsky, 1867). Together with his study of the development of urochordates (Kowalevsky, 1866; 1871), this introduced a new way of thinking about the relationship between the evolution and development of animals, and established the basis for longstanding theories of the evolutionary origin of vertebrates. Some one hundred and fifty years later, cephalochordates and urochordates are again in the spotlight, as molecular biology and genome sequencing promise further revelations about the origin of vertebrates. The work of the 2006 Kowalevsky Medal winner, Peter Holland (Fig. 1), has played a central role in their reinstatement (see Mikhailov and Gilbert (2002) for more details of the history of the Kowalevsky Medal). Here, I profile Peter Holland's contribution to the rebirth of Evolutionary Developmental Biology in general and the study of homeobox genes and vertebrate origins in particular.
