New molecular insight into vertebrate brain development

November 18, 2008

In the December 1st issue of G&D, Dr. Fred H. Gage (The Salk Institute for Biological Studies) and colleagues reveal a role for the Hippo signaling pathway in the regulation of vertebrate neural development, identifying new factors - and potential therapeutic targets - that may be involved in congenital brain size disorders and neurological tumor formation.

Their paper will be made available online ahead of print on 11/17 at http://genesdev.org

Establishing the basic embryonic brain requires the formation of a hollow neural tube, which serves as the rudimentary central nervous system, as well as the controlled proliferation and differentiation of neural progenitor cells into various specialized cell types.

The Hippo pathway is an ancient conserved signaling cascade that is known to regulate organ size in the fly and mouse. Previous research has demonstrated that Hippo signaling serves as a brake on cell growth and proliferation by preventing another protein, YAP, from entering the nucleus and activating pro-growth genes.

Drs. Xinwei Cao, Samuel Pfaff and Fred Gage now report that Hippo signaling is a critical master regulator of bran size in vertebrates that functions by restricting instructing the survival, proliferation and differentiation of neural precursor cells. In addition, the researchers identified the TEA domain (TEAD) transcription factor protein as the long-sought-after cognate DNA-binding partner of YAP in the nucleus.

Using genetic manipulation of chick embryos, the scientists demonstrated the consequences of altered Hippo signaling on vertebrate neural tube development. Increased YAP/TEAD activity induced neural progenitor cell overproliferation and the formation of an expanded neural progenitor cell population. Decreased YAP/TEAD activity led to increased cell death, while repression of YAP/TEAD target genes induced premature neuronal differentiation.

Owing to the evolutionary conservation of the Hippo signaling pathway, Dr. Gage states that "understanding the HIPPO path may bring insights to human brain malformations. There are a number of brain size defects for which we are considering a follow up, including microcephaly and Autism, where the overall brain size is affected but structures retain the proportionality. The function of the HIPPO pathway also has implications for brain size evolution, which is of great interested to us."

Cold Spring Harbor Laboratory

The Regulatory Mechanism of Warts and the Role of Hippo Pathway in Adult Stem Cell Proliferation in Drosophilia
by Yan Yan (Author)

This book summarizes the most recent discoveries of the novel tumor suppressor pathway - the Hippo pathway- in cancer research and somatic adult stem cell research. Besides the informative review of the genetics and molecular biology about the components, functions, and regulatory mechanisms of the Hippo pathway in the embryo development and adult stages, the future research directions of novel dWarts regulatory mechanism and the functions of the Hippo pathway in somatic adult stem cell were deliberated analyzed and designed. Thus this book will benefit to the scientists who are interested in genetics, developmental biology, cancers, stem cell research, and regenerative biology medicine.

Advances in Cancer Stem Cell Biology
by Roberto Scatena (Editor), Alvaro Mordente (Editor), Bruno Giardina (Editor)

In recent years, cancer stem cells have been recognized as important component in carcinogenesis and they seem to form the basis of many (if not all) tumor types. Cancer stem cells or "cancer cell like stem cells" have been isolated from various cancers of different origin (blood, breast, brain, skin, head and neck, thyroid, cervix, lung, retina, colon, pancreas and so on). Cancer stem cells - rare cells with indefinite proliferative potential that drive the formation and growth of tumours- seem to show intriguing relationships with physiological stem cells. Specifically, these cancer cells show significant similarities in the mechanisms that regulate self-renewal of normal stem cells. Moreover, tumour cells might directly arise from normal stem cells. Further, the cellular biology of...

International Review Of Cell and Molecular Biology, Volume 291
by Kwang W. Jeon (Editor)

International Review of Cell and Molecular Biology presents current advances and comprehensive reviews in cell biology--both plant and animal. Articles address structure and control of gene expression, nucleocytoplasmic interactions, control of cell development and differentiation, and cell transformation and growth. Impact factor for 2009: 6.088.* Authored by some of the foremost scientists in the field * Provides up-to-date information and directions for future research * Valuable reference material for advanced undergraduates, graduate students and professional scientists

Essentials of Stem Cell Biology, Second Edition
by Robert Lanza (Editor), John Gearhart (Editor), Brigid Hogan (Editor), Douglas Melton (Editor), Roger Pederson (Editor), E. Donnall Thomas (Editor), James Thomson (Editor), Sir Ian Wilmut (Editor)

First developed as an accessible abridgement of the successful Handbook of Stem Cells, Essentials of Stem Cell Biology serves the needs of the evolving population of scientists, researchers, practitioners and students that are embracing the latest advances in stem cells. Representing the combined effort of seven editors and more than 200 scholars and scientists whose pioneering work has defined our understanding of stem cells, this book combines the prerequisites for a general understanding of adult and embryonic stem cells with a presentation by the world's experts of the latest research information about specific organ systems. From basic biology/mechanisms, early development, ectoderm, mesoderm, endoderm, methods to application of stem cells to specific human diseases, regulation and...

Animal Models of Human Disease, Volume 100 (Progress in Nucleic Acid Reasearch)
by Min Kyung-Tai (Editor), Karen Chang (Editor)

Animal experiments have contributed much to our understanding of mechanisms of disease and are important for determining new therapies. This volume reviews the latest research and developments in this field. * Discusses new discoveries, approaches, and ideas * Contributions from leading scholars and industry experts * Reference guide for researchers involved in molecular biology and related fields

Cancer and Development, Volume 94 (Current Topics in Developmental Biology)
by Michael Dyer (Editor)

In recent years, a number of molecular pathways and cellular processes that are essential for normal vertebrate development have been implicated in cancer initiation and progression. In this volume, leaders in the field of cancer genetics and developmental biology share recent insights into the importance of developmental pathways for tumorigenesis. These discoveries provide important avenues for innovative new approaches to treating some of the most challenging developmental tumors.Provides researchers an overview and synthesis of the latest research findings and contemporary thought in the areaThere are now a large number of molecular targeted therapies for the treatment of cancer. Many of these therapies target pathways that are essential for normal development. Therefore, this volume...

Invertebrate and Vertebrate Eye Development, Volume 93 (Current Topics in Developmental Biology)
by Ross L Cagen (Series Editor), Thomas A. Reh (Series Editor)

Vision is our primary sensory modality and we are naturally curious as to how the visual system assembles. The visual system is in many ways remarkably simple, a repeating assemblage of neurons and support cells that parse the visual field through precision and redundancy. Through this simplicity the eye has often led the way in our exploration of how an organ is assembled. Eye development has therefore long been a favorite for exploring mechanisms of cell fate choice, patterning and cell signaling. This volume, which is part of the Current Topics in Developmental Biology series, highlights the exceptional advances over the past twenty yearsContributions from researchers who are active in identifying new paradigms to explore Review of our current state of knowledge Chapters written by...

The Sticky Synapse: Cell Adhesion Molecules and Their Role in Synapse Formation and Maintenance
by Michael Hortsch (Editor), Hisashi Umemori (Editor)

This is a comprehensive book on how adhesive proteins contribute to synapse formation, function, and remodeling. Topics covered range from general synaptic processes to CAM-specific chapters and how these CAM families contribute to synaptic functionality.

microRNAs in Development, Volume 99 (Current Topics in Developmental Biology)
by Eran Hornstein (Editor)

This new volume in the "Current topics in Developmental Biology" series concentrates on MicroRNAs in Development. It includes chapters on such topics as miRNA networks in neuronal development, let-7 in development, and Hox networks and miRNA. With an international team of authors, this volume is a must-have addition for researchers and students alike.Concentrates on MicroRNAs in Development. Includes chapters on such topics as miRNA networks in neuronal development, let-7 in development, and Hox networks and miRNA. With an international team of authors, this volume is a must-have addition for researchers and students alike.

Stem Cell Regulators, Volume 87 (Vitamins and Hormones)
by Gerald Litwack (Series Editor)

First published in 1943, Vitamins and Hormones is the longest-running serial published by Academic Press. The Editorial Board now reflects expertise in the field of hormone action, vitamin action, X-ray crystal structure, physiology and enzyme mechanisms. Under the capable and qualified editorial leadership of Dr. Gerald Litwack, Vitamins and Hormones continues to publish cutting-edge reviews of interest to endocrinologists, biochemists, nutritionists, pharmacologists, cell biologists and molecular biologists. Others interested in the structure and function of biologically active molecules like hormones and vitamins will, as always, turn to this series for comprehensive reviews by leading contributors to this and related disciplines. This volume focuses on stem cell regulators. ...