Bio 625, Developmental Genetics

Fall 2009, 512 Fordham Hall

Vicki Bautch (bautch@med.unc.edu; 6-6797)

Mark Peifer (peifer@unc.edu; 2-2271)

and graduate moderators listed below

http://www.bio.unc.edu/faculty/peifer/documents/Bio625-2009.htm

 

Week 0 Organization Meeting – Vicki Bautch and Mark Peifer

Aug. 27, 4 PM 512 Fordham Hall.  Overview of Course; Requirements; Pick day/time for weekly class meeting

 

Week 1 (8/31) Nathan Harris

Genevet A, Polesello C, Blight K, Robertson F, Collinson LM, Pichaud F and Tapon N. (2009). The Hippo pathway regulates apical-domain size independently of its growth control function. J Cell Sci 122, 2360-2370.

This paper reveals a new role for a pathway previously associated with growth control.  Here they show that cell polarity is influenced by Hippo signaling.  Since loss of cell polarity is a feature of invasive tumors, Hippo may influence tumor invasion.

 

Week 2 (9/7) Kim Peters

Choe CP, Brown SJ. (2007) Evolutionary flexibility of pair-rule patterning revealed by functional analysis of secondary pair-rule genes, paired and sloppy-paired in the short-germ insect, Tribolium castaneum. Dev Biol. 302:281-94

This paper examines evolutionary relationships in the function of genes important for the development of all organisms. Insects form segments using a group of genes called pair-rule, and here they show that many functions of a subset of these genes are conserved between widely divergent insects. However there are some differences that suggest overall flexibility in the patterning system.

 

Week 3 (9/14) Jean Davidson

Chera S, Ghila L, Dobretz K, Wenger Y, Bauer C, Buzgariu W, Martinou J-C, Galliot B. (2009). Apoptotic cells provide an unexpected source of Wnt3 signaling to drive Hydra head regeneration. Dev Cell 17, 279-289.

This paper provides the first molecular pathway for regeneration of a whole structure – the head of the freshwater polyp Hydra.  Apoptotic cells release Wnt3, which is necessary and sufficient for head regeneration, even when expressed in non-head regions.  Hydra are the classic species for regeneration studies, and this work has implications for regeneration of mammalian organs and limbs.

 

Week 4 (9/21) Erin Kaltenbrun

Kragl M, Knapp D, Nacu E, Khattak S, Maden M, Epperlein HH, Tanaka EM. (2009). Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature 460, 60-67.

Alvarado AS. (2009). A cellular view of regeneration. Nature 460, 39-40 [News and Views].

This paper also addresses an important question in regeneration: as a complex structure such as a limb regenerates how do the cells know where to position themselves so that bone is inside and skin is outside?  Surprisingly, this work shows that the edge of the amputed limb does not completely de-differentiate, but rather forms distinct pools of progenitor cells that in some cases retain their positional identity within the limb.  Axolotls are salamanders, and they and other salamanders can fully reconstitute functional limbs after injury.

 

Week 5 (9/28) David Wiley

Little SC, Mullins MC. (2009). Bone morphogenetic protein heterodimers assemble heteromeric type I receptor complexes to pattern the dorsoventral axis. Nat Cell Biol 11, 637-643. [plus Supplemental Figures and Information].

This paper investigates the players involved in an important signaling pathway that affects embryonic patterning, the BMP pathway.  They show that one aspect of patterning, dorsoventral (back-belly), requires a ligand that is a mixture of two types of BMPs in the zebrafish.  This suggests how BMP signaling can occur in the presence of antagonists that are also expressed, and helps in better understanding the regulation of this pathway.

 

Week 6 (10/5) Tangi Smallwood

Curran K, Raible DW, Lister JA. (2009). Foxd3 controls melanophore specification in the zebrafish neural crest by regulation of Mitf. Dev Biol 332, 408-417.

Quigley IK, Parichy DM. (2002). Pigment pattern formation in zebrafish: a model for developmental genetics and the evolution of form. [Review].

This paper describes a mechanism whereby cells adopt either a melanophore fate or the fate of other colored chromophores in the zebrafish.  They show that foxd3 represses melpanophore fate and is a negative regulator of a locus that can be oncogenic in humans, Mitf.  They suggest that this pathway might be relevant to human melanoma.

 

Week 7 (10/12) Stephanie Notowarski

Wang X-P, O'Connell DJ, Lund JJ, Saadi I, Kuraguchi M, Turbe-Doan A, Cavallesco R, Kim H, Park PJ, Harada H, Kucherlapati R, Maas, RL. (2009). Apc inhibition of Wnt signaling regulates supernumerary tooth formation during embryogenesis and throughout adulthood. Development 136, 1939-1949.

This paper describes a signal, Wnt, that is necessary and sufficient for tooth formation from the jaw.  Surprisingly, the signal is produced by a small number of cells that then "organize" the surrounding tissues to form the tooth layers and support structures.  These findings suggest that we may be able to “regenerate” replacement teeth in the future! (STARTING THE HALLOWEEN THEME OF "STRANGE BUT TRUE"!)

 

(10/19) NO CLASS - FALL BREAK

 

Week 8 (10/26) Soren Johnson

Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA. (2005). Rejuventation of aged progenitor cells by exposure to a young systemic environment. Nature 433, 760-764.

This paper utilizes a technique called "parabiosis" whereby two mice are joined so that they share their circulatory system!  This work shows that stem and progenitor populations in several organs that decline with age can be"rejuvenated" by exposure to circulation from a younger mouse.  This work indicates that age-dependent circulating factors contribute to maintenance stem and progenitor pools. (CONTINUING THE HALLOWEEN THEME OF "STRANGE BUT TRUE"!)

 

 

Week 9 (11/2) Amanda Wisz

Pereira JP, An J, Xu Y, Huang Y, Cyster JG. (2009) Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids.
Nat Immunol. 10:403-11.

This paper investigates the mechanisms that allow immature B cells to accumulate in a niche in the bone marrow sinusoids. This niche is between the site of synthesis and the final site of release of these blood cells from the bone marrow, and seems important for maturation. A specific integrin and a G-protein coupled receptor are involved in the B cell accumulation, and the significance is both for blood cell maturation and perhaps for trafficking of tumor cells.

Review 1

Review 2

 

Week 10 (11/9) Deirdre Tatomer

Kim KW, Nykamp K, Suh N, Bachorik JL, Wang L, Kimble J. (2009). Antagonism between GLD-2 binding partners controls gamete sex. Dev Cell 16, 723-733.

This paper investigates the interesting question of how gametes are determined as male or female in the worm C. elegans.  C. elegans is a hermaphrodite, and gamete production begins with sperm that transitions to oogenesis (eggs).  Here they show that this shift is associated with the selective association of GLD-2, part of a poly(A) polymerase complex, with distinct binding partners.  The significance is that the model of combinatorial control of developmental processes shown here is widely used, and GLD-2 is implicated in memory control in mammals.

 

(11/23)  NO CLASS THANKSGIVING

 

Week 11 (11/16) Minna Roh

Munro E, Nance J, Priess JR. (2004). Cortical flows powered by asymmetrical contration transport PAR proteins to establish and maintain anterior-posterior polarity in the early C. elegans embryo. Dev Cell 7, 413-424.

This paper describes how symmetry is “broken” in the early C. elegans embryo, to set up the two different daughter cells that will result from the first cell division.  The sperm entry point has destabilized actomyosin contractile network that initiates flows that act to localize polarity proteins on one side or the other of the single cell embryo prior to mitosis.  This work has implications for how asymmetric cell divisions are regulated to maintain stem cell compartments while also producing daughter cells that go on to differentiate, and how this process may be mis-regulated in disease.

 

Week 12 (11/30) Luciana Leopold

Wang MC, O'Rourke EJ, Ruvkun G. (2008) Fat metabolism links germline stem cells and longevity in C. elegans. Science 322:957-60.

This paper illustrates what model organisms can tell us about fat and the control of aging, which is in the news extensively right now. Here fat metabolism and aging are also linked to reproduction, and germ cell arrest induces a lipase that leads to lean and long-lived worms. This work has implications for the decline in adult stem cells that is associated with aging and compromises tissue regeneration with time.

 

Week 13 (12/7) FINAL EXAM